NZ216830A

NZ216830A - Carboxylic acid derivatives and pharmaceutical compositions

Info

Publication number: NZ216830A
Application number: NZ216830A
Authority: NZ
Inventors: Hans Peter Wolff; Ernst-Christian Witte; Hans-Frieder Kuhnle
Original assignee: Boehringer Hannheim Gmbh
Priority date: 1985-07-16
Filing date: 1986-07-14
Publication date: 1990-11-27
Also published as: FI871143A0; PT82987B; NO871059D0; CA1316922C; NO166939C; WO1987000521A3; ZA865192B; NO871059L; ES2001163A6; PT82987A; DE3525284A1; NO166939B; WO1987000521A2; DK100487D0; DD254193A5; EP0226636B1; AU5988086A; DK100487A; IL79379A0; US4933367A

Abstract

PCT No. PCT/EP86/00406 Sec. 371 Date Mar. 12, 1987 Sec. 102(e) Date Mar. 12, 1987 PCT Filed Jul. 10, 1986 PCT Pub. No. WO87/00521 PCT Pub. Date Jan. 29, 1987.This invention relates to carboxylic acid derivatives and their use thereof. The compounds are useful in treatment of various diseases such as diabetes, prediabetic conditions, adipositas ailments or atherosclerosis.

Description

<div class="application article clearfix" id="description"> New Zealand Paient Spedficaiion for Paient Number £16830 NO DRAWING! Complete Specification Filed: ^^"7. Class: . Co?j!<?vSr7/^.Sj-y. Publication Date: P.O. Journal, No: .... j Class Cont: 13. tS) .jo^ lb;.,.. Class Cont:^QT^).^1Z./a?,AQj^fl,(^ 5vjv>77 j j4>i ... Class Cont: -i. • NEW ZEALAND r> a- 1 n c -> n.z. no. COMPLETE SPECIFICATION NEW CARBOXYLIC ACID DERIVATIVES, PROCESSES PREPARATION THEREOF, THE USE THEREOF AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM We, BOEHRINGER MANNHEIM GmbH, a company of the Federal Republic of Germany of 6800 Mannheim 31, Federal Republic of Germany, do hereby declare the invention, for which we pray that a Patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement:- - 1 - The present invention is concerned with new carboxylic acid derivatives, processes for the preparation thereof, the use thereof and pharmaceutical corrqpositions containing them. \ The new carboxylic acid derivativfes according to the present invention are compounds of the general formula:- ?2 R, - A - C - COOH (I) I X wherein R^ is an optionally substituted aryl or aryloxy radical, R2 is a hydrogen atom, a lower alkyl radical or an R-^-A- radical and, when X is a cyano group, R2 can also be an acylamino or amino radical, A is a straight-chained or branched, saturated or unsaturated alkylene radical containing 3 to 8 carbon atoms which has a chain length of at least 3 carbon atoms, X is a cyano group or a radical of the general formula -B-R^ or -D-NR4R5# in which B is 0, S, SO, S02, 0(C0), 0S02# NHCO, NHSO2 or CO, D is a valency bond, S02 or CO, Rg is an alkyl, trifluoromethyl, cycloalkyl, aralkyl, aralkenyl or aryl radical, the aryl moieties of which are optionally substituted,- R^ is a hydrogen atom, a lower alkyl radical or an optionally substituted aryl or aralkyl radical, Rj is a hydrogen atom or a lower alkyl radical or R^ and R^ together form an alkylene -3- chain containing 4 to 6 carbon atoms which can be interrupted by 0, S or NRg and Rg is a hydrogen atom, a lower alkyl radical or an optionally substituted phenyl or benzyl radical, as well as the physiologic-5 ally acceptable salts, esters, amides and nitriles thereof, with the proviso that: a) when A is an alkylene radical with 3 carbon atoms, al) in all cases, an aryl radical is not an unsubstituted phenyl radical and 10 a2) X is not -CN, -NHCORg or -NR4R57 b) when X is a methylthio radical, R2 is not a methyl radical: c) when X is -NH2 or -NHC0CH3, Rj^- is not 4-phenyl- butyl or 4-(4-methoxyphenyl)-butyl; 15 d) when X is 2,4-dinitrophenyl, R^A- is not 4-phenyl-butyl or 5-phenylpentyl; and e) when X is -COCH^, Rj_A is not 3-(2-chlorophenyl)-propyl or 5-(4-methoxyphenyl)-pentyl. Of the compounds of general formula (I), with 20 the exception of norvaline analogues (A = and X = NR^Rg or NHCOR3), hitherto only a few examples are known. The pharmacological action of the compounds according to the present invention has hereby not been described: 25 2-cyano-5-phenylpentanoic acid, as well as derivatives with substituents in the aromatic ring, have been described as reaction products (Pallaud et al., C.R. Acad. Sci., Ser. C, 273, 711/1971). 2-cyano-7-phenylheptanoic acid has also been described as a reaction product (Julia et al., Bull. Soc. Chint. Fr., 1968, 3691). 2-phenoxy-5-phenylpentanoic acid (U.S. Patent Specification Ho. 3,562,330) has been described as a precursor of anti-arrhythmically-active amines; methyl 5-phenyl-2-phenylsulphonylpent-4-enoate has been described as an intermediate (Trost and Hung, J.A.C.S., 105. 7757/1983): 2-methyl-2-methylthio-5-phenylpentanoic acid and phenyl-substituted analogues, as well as 2-methyl-2-methylthio-6- (3-methoxyphenyl) -hexanoic acid and 2-methyl- 2-methyl-thio-7- (3,4-methylenedioxyphenyl) -heptanoic acid have been described as intermediates for the preparation of enol thioethers (Trost et al., J. Org. Chem., 43, 4549/ 1978). Besides the already-mentioned norvaline analogues (A = -(0112)2")' the following have also already been described as derivatives with an amino function: a) 2-amino-6-phenylhexanoic acid and its N-acetyl derivative (Pattabiraman et al., Biochem. J., 126, 645/ 1972). Hashimoto et al. , Int. J. Pept. Protein Res., 21, 11/1983: b) 2-amino-6-(4-methoxyphenyl)-hexanoic acid aripl,- irtfs^ fy "■ -7K0VI989 N-acetyl derivative (Kosui et al., Bull. Chem. Soc. Japan, 55_, 918/1982; Mihara et al., Int. J. Pept. Protein Res., 23, 447/1984); c) 2-[(2,4-dinitrophenyl)-amino]—6-phenylhexanoic acid and 2-[(2,4-dinitrophenyl)-amino]-7-phenylheptanoic acid (Kawai et al., Tetrahedron Lett., 1975, 2845; Tetrahedron, 34, 3435/1978); d) 2-arylsulphonylamino-5-phenvlpentanaiG acids with 4-cyanochenyl as the aryl radical (Yieweg and Wagner, Pharmazie, 38, 22/1983) and with 4 -methylpheny 1 and 1-naphthyl as the aryl radical (Vieweg and Wagner, Pharmazie, 3£, 818/1983). The two last-mentioned compounds are intermediates for the preparation of potential serine proteinase inhibitors; e) 2-acetyl-5-phenylpentanoic acid (Ansell et al., J. Chem. Soc., Perkin Trans., 1, 2789/1973 and 2-acetyl-5-(2-chlorophenyl)-pentanoic acid (European Patent Specification No. 0,025,192), the latter serving for the preparation of antidiabetically-active substances. However, no pharmacological action was attributed to the intermediate. f) 2-acetyl-7-(4-methoxyphenyl)-heptanoic acid has been described as a reaction product (Atkinson and Green, J. Chem. Soc. Perkin Trans., 1, 394/1974); g) ethyl 2-acetoxy-5-phenylpentanoate (Chottard et al., Tetrahedron, 25, 4967/1969), as well as 2-aminocarbonyl-5-phenylpentanoic acid (Gardner and Brandon, J. Org. Chem., 22, 1704/1957) as reaction products. The compounds of general formula (I) possess valuable pharmacological properties. They can be used for the treatment of diabetes, prediabetes and especially for the treatment of mature diabetes. The compounds of general formula (I) have no relationship to known antidiabetic compounds either structurally or in the nature of their action. They lower the blood sugar level by an increase of the peripheral glucose oxidation, their action depending upon an increase of the sensitivity of peripheral tissues towards insulin. In contradistinction to the r biguanides, no increase of the blood lactate values is observed. Therefore, the compounds of general formula (I) are also valuable for the treatment of non-diabetic illnesses in which an insulin-resistance is present, for example adipositas and athersclerosis. We have also found that the anti-diabetic effectiveness is not limited to the new compounds of general formula (I) with the above-given meanings for R^, Rj# A and X but that derivatives of the following general formula (I1) also possess this newly found effectiveness. Thus, the present invention also provides pharmaceuticals for the treatment of diabetes, prediabetes, adipositas and athersclerosis which contain carboxylic acid derivatives of the general formula:- -7- 216830 o R,2 I R*, - A1 - C - COOH (I■) A I X' wherein R^ is a hydrogen atom or an optionally substituted aryl or aryloxy radical, R'? is a hydrogen mherein R'| has thfr meaning give above, Qj atom, a lower alkyl radical or an R^-A'- radical] and, 5 when x'is a cyano group, R'2 can also be an acylamino or amino radical, A1 is a straight-chained or branched, saturated or unsaturated alkylene radical containing up to IS carbon atoms, X* is a cyano or carbethoxy radical or a. radical of the general formula -B-R3 or -D-NR^R^, 10 in which B is 0, S, SO, S02, O(CO), 0S02, NHCO, NHS02 or CO and D is a valency bond, S02 or CO, R^ is an alkyl, trifluoromethyl, cycloalkyl, aralkyl, aralkenyl or aryl radical, the aryl moieties of which can be ^ substituted, R^ is a.hydrogen atom, a lower alkyl 15 radical or an optionally substituted aryl or aralkyl radical and is a hydrogen atom or a lower alkyl radical or and R^ can together form an alkylene l(2) chain containing 4 to 6 carbon atoms Which can be »• i interrupted by O, S or NRg and Rg is a hydrogen atom, 20 a lower alkyl radical or an optionally substituted phenyl or benzyl radical, as well as their phsyiolog-ically acceptable salts, esters, amines cfcd^nitriles. Aryl radicals are to be understood to be aromatic hydrocarbon radicals containing 2.1 6 8 o 0 -8- carbon atoms, phenyl and naphthyl radicals being preferred. By substituted aryl radicals are to be understood, in all definitions, those aromatic hydrocarbon radicals containing 6 to 14 carbon atoms which have, in one or more positions, hydroxyl, halogen, lower alkyl, having up to 4 carbon atoms, lower alkoxy having up to 4 carbon atoms, trifuoromethyl, cyano, nitro or amino, optionally substituted once or twice by lower alkyl having up to 4 carbon atoms. In particular, there are preferred phenyl and naphthyl radicals optionally substituted by the above-mentioned groups, the phenyl and 4-chlorophenyl radicals being especially preferred. By halogen, there is to be understood fluorine, chlorine, bromine and iodine and preferably fluorine, chlorine and bromine. The aryloxy radical contains an aromatic hydrocarbon moiety with 6 to 14 carbon atoms and preferably a phenyl radical. By substituted aryloxy radicals, there are to be understood those which are substituted in the same way as the above-mentioned aryl radicals, the 4-chlorophenoxy radical being preferred. By unbranched alkylene chains A, there are preferably to be understood the following: -(CH2)n- , n in general formula 1=3-8, -CH=CH.CH2-n in general formula I' = 1 - 18, -CziC.CH^-As branched radicals A, there are especiall preferred -CH2-CH.CH2- and -CH=C.CH2- cu3 ch3 By alkyl radicals are to be understood straight-chained and branched hydrocarbon chains containing up to 8 carbon atoms, the methyl and octyl radicals being especially preferred. Cycloalkyl radicals R^ can contain 5 to 7 carbon atoms in the ring system, the cyclohexyl radical being preferred. By aralkyl and aralkenyl radicals R^ are to be understood saturated and unsaturated alkyl radicals containing up to 4 carbon atoms which are substituted by an optionally substituted aryl radical as defined hereinbefore. Preferred amongst these are the 2-phenyl-ethyl and 2-phenylethenyl radicals. By lower alkyl radicals R^, Rg and Rg are to be understood hydrocarbon radicals containing up to 4 carbon atoms, the methyl and ethyl radicals being preferred. By aralkyl radicals R^ and Rg are to be understood alkyl radicals containing up to 3 carbon atoms which are substituted by an optionally substituted aryl radical as defined hereinbefore, the benzyl radical being preferred. By a radical -NR^R^ in which the symbols R^ and Rg together form an alkylene chain which can be interrupted by 0, S or NRg, there are to be understood saturated nitrogen heterocycles with 5 or 6 ring atoms which, in any desired positions, can additionally -10- contain an oxygen, sulphur or nitrogen atom. Preferred amongst these are to be understood the piperidino, morpholino, 5-methylpiperazino, 5-phenylpiperazino and 5-benzylpiperazino radicals. By a group of the general formula -b-r^ or -D-NR^Rg are preferably to be understood the following: -cu, -cooc2h5, -och3, -sch3, -soch3# -so2ch3, -so2cf3, -0-phenyl, -S-phenyl, -SO-phenyl, -S02~phenyl, -SO 2~naphthyl, -SO2CH2CH2-phenyl, -SO2-CH=CH-phenyl, -ococh3, -oso2ch3, -nhcoch3, -nhso2ch3, -coch3, -OCO-phenyl, -0S02~phenyl, -NHCO-phenyl, -NHS02-phenyl, -CO-phenyl, -NH2, -N(C2Hg)2< -NH-phenyl, -NH-benzyl, morpholino, piperidino, 4-benzylpiperazino, -S02NH2, -S02N(C2Hg)2, -S02~piperidino, -CONH2, -CON(CH3)2, -C0-N(C2H5)2, -CO-NH-phenyl, -CO-NH-phenyl, -CO-piperidino, -CO-morpholino, -C0-(4-phenylpiperazino) and -CO-(4-benzylpiperazino), whereby the phenyl ring can, in all cases, be substituted by the above-mentioned substituents. It is obvious that in the case of an unsaturated allcylene chain A, an aryloxy substituent possibly present must be separated from the double bond by at least one saturated carbon atom since otherwise the Rj^-A— radical would be understood to include reactive enol ethers. As physiologically acceptable salts, there are especially preferred the alkali metal, alkaline earth -11- metal and ammonium salts, as well as possibly salts with blood sugar-lowering biguanides. The esters derived from the carboxylic acids of general formula (I) contain, as alcohol component, lower monohydroxy alcohols, of which methanol, ethanol and n-butanol are preferred, as well as polyhydroxy alcohols, for example glycerol, or alcohols with other functional groups, for example ethanolamine. The amides according to the present invention derived from the carboxylic acids of general formula (I) contain, as amine component, preferably ammonia, £-aminobenzoic acid, P-alanine, ethanolamine or 2-aminopropanol. However, there can also be used alkyl-amines, for example isopropylamine or tert. -butylamine, di alkyl amines, for example diethylamine, as well as cyclic amines, for example morpholine or 4-substituted piperazines. The substituted carboxylic acids of general formula (I) have a centre of chirality. Therefore, the above definitions of the compounds according to the present invention also include all possible enantiomers, mixtures thereof and the racemates. The present invention also provides a process for the preparation of the compounds of general formula (I), wherein A) in per se known manner, a compound of the general formula:- -12- H - C - W (II) Z 2 in which Z^ is -COORy, -CN, -CO-R^, -SO-Rg, -S02~R3, -CONH2 or -S02NH2, Z2 is a hydrogen atom, a lower alkyl radical or -NH-Rg, W is -COOR^ or another group which can be converted into the carboxyl function, R^ is a lower alkyl radical, Rg is an amino protective group and R2 has the same meaning as above a 1) is alkylated with a compound of the general formula:- in which R^ and A have the above-given meanings and Y is a reactive residue; or a 2) when Z2 is a hydrogen atom, is condensed with a compound of the general formula:- in which A' is an alkylene radical A shortened by one CH2 group and R^ has the above-given meaning, and, subsequent to the condensation, the resuitant double bond is hydrogenated and b) the compounds of the general formula:- Rx - A - Y (III) R1 - A' - CHO (III') Rx - A - C - W (IV) o OC -13- obtained from the above-mentioned process steps are optionally converted in that, for example © b 1) when Zj is a hydrogen atom, they are again alkyl ated with a compound of the general formula:- 5 R2 " Y ^ G in which R2 has the above-given meaning and Y is a reactive group; or b 2) when Z1 is -COORy and Z2 is -NH-Rg, the substit-uent Rg is converted in per se known manner into an 10 -CO-R^ or -S02-R3 radical; or b 3) when Z^ is COOR^ and Z2 is a hydrogen atom, the hydrogen atom is replaced in per se known manner by a halogen atom using a halogenation agent, whereafter the radical is converted by decarboxylation into a 15 hydrogen atom and the reactive derivative (IV), in r~s which Z- is a halogen atom and Z, is a hydrogen atom, is reacted either with a compound of the general formula:- H - B - R3 (VI) 20 in which B is 0, S or NHS02 and R^ has the above-given meaning, to give a compound of the general formula:- H I R, - A - C - W (IV1 ) I B - R3 or with a compound of the general formula:- -14- (VI • ) in which and R^ have the above-given meanings, to give a compound of the general formula and c) subsequent to the condensation, for the case in which c 1) B is a sulphur atom, it is oxidised in per se known manner to give the corresponding sulphoxide or sulphone; or c 2) when in the reactive derivative (IV) Z-^ is a hydrogen atom and Z2 is a halogen atom, it is reacted with sodium sulphite and the compound obtained of general formula (IV), in which Z2 is now -SO^H, is converted in per se known manner into the -SOjNR^Rg group and subsequent to this conversion possibly carried out of the compound (IV), the group W and optionally Z^ are converted into the free carboxylic acids or into the salts, esters or amides thereof. B) A further process for the preparation of compounds of general formula (I) consists in that a compound of general formula (IV), wherein Z1 and Z2 together represent an oxo function, is first reacted with a reducing agent or with an organometallic compound of the general formula H R1 - A - C - W (IV") -15- I 3*2 - M (VII) in which R2 has the above-given meaning and M is an i alkali metal or alkaline earth metal, and the compound obtained of general formula (IV), in which is now a radical of the formula R2 and Z2 is a hydroxyl group, is acylated with a sulphonyl chloride of the general formula R3 - S02C1 (VIII) or with a carboxylic acid chloride of the general formula:- R3 - C0C1 (IX) in which R3 has the above-given meaning, and subsequently thereto, the group W is optionally converted into a free carboxylic acid or a salt, ester or amide thereof. In the case of alkylations according to process a 1), as reactive derivative (III) there is used either a halide, especially a chloride or bromide, or an appropriate sulphonic acid ester, for example a mesylate or tosylate. The reaction of the halides or sulphonic acid esters with the compounds of general formula (II) preferably takes place with the addition of a strong base, for example sodium ethylate, sodium hydride or l,8-diazabicyclo(5,4,0)undec-7-ene. The reaction can -16- be carried out in an inert solvent, for example ethanol, dimethyl sulphoxide or benzene. Furthermore, as solvent, there can also be used, for example, dimethylformamide or hexamethylphosphoric acid triamide. The reaction is preferably carried out at temperatures ranging from ambient temperature up to the boiling temperature of the solvent used. The reaction of the compounds (II) with aldehydes of general formula (III1) according to process a 2) takes place under conditions which are usual for a condensation of activated methylene groups with keto compounds. The condensation is preferably carried out in pyridine or dimethylformamide with the addition of a catalytic amount of a strong base, for example piperidine An appropriate solvent, for example benzene, is preferably added to the reaction mixture in order to be able to distil off the reaction water azeotropically. The subsequent hydrogenation of the resultant double bond is carried out in the usual way with catalytically activated hydrogen at normal pressure or under an increased pressure. As catalysts, there can be used metal catalysts, for example Raney nickel or palladium-charcoal. As solvents, there can be used, for example, acetic acid or lower alcohols and, in the case of carboxylic acids (IV), aqueous alkali can also be used. -17- By an amino protective group is to be understood, for example an acyl radical, such as a formyl or acetyl radical. However, other protective groups can be used, for example those used in peptide chemistry. For the conversion of a compound of general formula (IV) with a protected amino group (Zj_ = -NH-Rg) into a derivative (IV) (Z^ = -NH-SC^-Rg)/ the group Rg is first split off in the usual way, for example in the case of acyl radicals by saponification with a dilute aqueous alkali metal hydroxide solution or with a dilute mineral acid. Subsequently, the free amino acid obtained, preferably after protection of the carboxyl function, for example by esterification, is acylated in the usual way by means of a sulphonyl chloride of general formula (VIII). In the case of aromatic sulphonyl chlorides, the reaction can also be carried out according to the Schotten-Baumann reaction. If it is desired to work under anhydrous conditions, it is preferable to use anhydrous pyridine. However, other tertiary bases can also be used, for example, dimethyl-aniline or triethylamine, in an inert solvent, for example methylene chloride. Instead of the free amino acids, their salts can also be used. For the halogenation of compounds of general formula (IV), in which Z2 is a hydrogen atom, it is especially preferred to use sulphuryl chloride, N-chlorosuccinimide or N-bromosuccinimide. Reactions -18- with N-chloro- or N-bromosuccinimide are preferably carried out in an inert solvent, for example tetra-hydrofuran, at ambient temperature or at a moderately increased temperature. The reaction preferably takes place with the addition of a strong base, for example sodium hydride. Reactions with sulphuryl chloride preferably take place without the use of solvents at an elevated temperature, preferably at 50 to 80°C. The decarboxylation of compounds of general formula (IV), wherein W and Z^ are -COOR^ groups, is preferably carried out with saponification of the appropriate ester according to known processes. The decarboxylation is preferably carried out in a mixture of 6N hydrochloric acid and glacial acetic acid or in aqueous sodium hydroxide solution at the boiling temperature. The reaction of the a-halogenocarboxylic acids of general formula (IV), wherein is a hydrogen atom and Zj is a halogen atom, with the compounds of general formula (VI) preferably takes place with the addition of an acid-binding agent, for example sodium hydrogen carbonate, sodium carbonate, potassium carbonate, sodium ethylate or sodium hydride. Esters of the a-halo acids are preferably used for the reaction. As inert solvent for the reaction, there can be used, for example, diethyl ether, benzene, tetrahydrofuran, dioxan or methylene chloride. In the case of the use of inorganic -19- bases, as reaction medium there can also be used, for example, ethanol, butan-2-one, dimethylformamide, hexamethylphosphoric acid triamide or acetonitrile. The reactions are carried out at ambient temperature or with heating and preferably at the boiling temperature. The oxidation of compounds of general formula (IV1), in which B is a sulphur atom, to give sulphoxide s or sulphones is preferably carried out with hydrogen peroxide in a polar solvent, for example glacial acetic acid, a mixture of glacial acetic acid and acetic anhydride or acetone. The oxidation with trifluoroperacetic acid has proved to be especially preferable. As solvent, there is hereby preferably used trifluoroacetic acid. The reaction of compounds of general formula (IV), in which is a hydrogen atom and Zj is a halogen atom, with sodium sulphite is carried out in per se known manner by heating the components in aqueous solution. The sulphocarboxylic acids obtained are converted in the usual way, for example with thionyl chloride, into the reactive sulphochlorides and these are then reacted with ammonia to give the desired ami do sulphonyl de ri vati ve s. The reduction of compounds of general formula (IV), in which and Z2 together signify an oxo group, according to process B can be carried out in the usual -20- way with catalytically activated hydrogen. There is hereby preferred a hydrogenation at normal pressure or under elevated pressure in the presence of a metal catalyst, for example palladium or Raney nickel, in a solvent, for example acetic acid or a lower alcohol. It is also possible to reduce with complex metal hydrides, sodium borohydride preferably being used. In this case, the reaction can be carried out in an alcohol, especially in methanol, or in dioxan or in an aqueous alkaline medium. The reaction of compounds of general formula (IV), in which and Z2 together signify an oxo function, with organometallic compounds of general formula (VII) according to process B takes place in an inert solvent, for example diethyl ether or tetrahydrofuran. The subsequent acylation of the resulting compounds (IV), in which Z^ is now R2 and Z2 is a hydroxy 1 group, with a compound of general formula (VIII) is carried out according to methods such as have already been described above for the acylation of amino acids. The reaction is preferably carried out in pyridine as solvent. By a group W which can be converted into a carboxyl function, there is to be understood, in particular, a nitrile group or a residue which can be oxidatively converted into a carboxyl function. As oxidisable groups, there are preferred the hydroxymethyl, -21- aminomethyl and formyl groups or functional derivatives of these groups. The oxidation can be carried out with conventional oxidation agents, for example manganese XV compounds, permanganates, dichromates and, in the case of the formyl group, also atmospheric oxygen and silver oxide. The conversion of the substituents W and possibly to be carried out after the condensation to give compounds of general formula (IV) takes place, for example, by saponification of carboxylic acid esters to the corresponding carboxylic acids with a mineral acid or an alkali metal hydroxide in a polar solvent, for example water, methanol, ethanol, dioxan or acetone. The saponification is preferably carried out with a strong base, for example sodium or potassium hydroxide, in a mixture of methanol and water at ambient temperature or at a moderately elevated temperature. On the other hand, however, carboxylic acids can be esterified in conventional manner or esters with a particular residue can be converted into esters with a different residue R^ by transesterification. Ester-ification of the carboxylic acids is preferably carried out in the presence of an acidic catalyst, for example hydrogen chloride, sulphuric acid, £-toluenesulphonic acid or a strongly acidic ion exchanger resin. Trans-esterifications, on the other hand, require the addition of a small amount of a basic substance, for example of z€Sm; I''' '■ \ o 218830 -22- an alkali metal or alkaline earth metal hydroxide or of an .alkali metal alcoholate. For the esterification of the carboxyl group or for a transesterification, there can, in principle, be used all alcohols. It is 5 preferred to use lower monohydroxy alcohols, for example methanol, ethanol or propanol, as well as poly-(T) hydroxy alcohols, for example glycerol, or alcohols with other functional groups, for example ethanolamine. The amides according to the present invention 10 derived from the carboxylic acids of general formula (I) are preferably prepared by per se known methods from the carboxylic acids or the reactive derivatives thereof, for example carboxylic acid halides, esters, azides, anhydrides or mixed anhydrides, by reaction with amines. 15 As amine components, there can be used, for example, ammonia, alkylamines and dialkylamines but also amino-alcohols, for example ethanolamine and 2-aminopropanol, as well as amino acids, for example 2-aminobenzoic acid, p-alanine- - Other valuable amino components 20 include, for example, alkyl-, aralkyl- and aryl-piperazines. Howeverthe preparation of the above amides can also take place by partial saponification of the nitriles derived from the carboxylic acids according to the 25 present invention. The saponification takes place in dilute mineral acids at a moderately elevated temperature, in alkaline hydroperoxide solution or advantage- ^ , v" 7H°Vt989 ously in 98% sulphuric acid or polyphosphoric acid. For the preparation of salts with pharmacologically acceptable organic or inorganic bases, such as sodium hydroxide, potassium hydroxide, calcium hydroxide, ammonium hydroxide, methylglucamine, morpholine or ethanolamine, the carboxylic acids can be reacted with the appropriate bases. Mixtures of carboxylic acids with appropriate alkali metal carbonates or hydrogen carbonates can also be considered. For the preparation of pharmaceutical compositions, the compounds of general formula (I) are mixed in known manner with appropriate pharmaceutical carrier substances, aroma, flavouring and colouring materials and formed, for example, into tablets or dragees or, with the addition of appropriate adjuvants, suspended or dissolved in water or an oil, for example olive oil. The compounds of general formula (I) can be administered orally or parenterally in liquid or solid form. As injection medium, there is preferably used water which contains the stabilising agents, solubilis-ing agents and/or buffers usual in injection solutions. Additives of this kind include, for example, tartrate and borate buffers, ethanol, dimethyl sulphoxide, complex formers (such as ethylenediamine-tetraacetic acid), high molecular weight polymers (such as liquid polyethylene oxide) for viscosity regulation or polyethylene derivatives of sorbitan anhydrides. -24- Solid carrier materials include, for example, starch, lactose, methyl cellulose, talc, highly dispersed silicic acid, high molecular weight fatty acids (such as stearic acid), gelatine, agar-agar, calcium phosphate, magnesium stearate, animal and vegetable fats and high molecular weight polymers (such as polyethylene glycols). Compositions suitable for oral administration can, if desired, contain flavouring and sweetening agents. The dosage administered depends upon the age, state of health ,and weight of the recipient, the extent of the disease, the nature of further treatments possibly carried out simultaneously, the frequency of the treatment and the nature of the desired action. Usually, the daily dosage of the active compound is from 0.1 to 50 mg./kg. of body weight. Normally, 0.5 to 40 and preferably 1.0 to 20 mg./kg./day in one or more administrations per day are effective in order to achieve the desired results. Apart from the compounds mentioned hereinafter in the Examples, as well as the esters and amides thereof, the following compounds are also preferred according to the present invention: 2-[(4-methylphenyl)-sulphonyl]-8-phenyloctanic acid 2- [ (4-me thylphenyl) -sulphonyl ] -5-phenylpent-4-ynoic acid 6- (4-methylphenyl) - 2- [ (4-me thylphenyl) - sulphonyl ] -hexanoic acid -25- 7-(4-methylphenyl)-2-[(4-methylphenyl)-sulphonyl]-heptanoic acid 8-(4-methylphenyl)-2-[(4-methylphenyl)-sulphonyl]-octanoic acid 10- (4-methylphenyl) - 2- [ (4-methylphenyl) - sulphonyl ] -decanoic acid 7-(4-chlorophenyl)-2-(amidosulphonyl)-heptanoic acid 7-(4-chlorophenyl)-2-(phenoxy)-heptanoic acid 7-(4-chlorophenyl)-2-(4-methylphenoxy)-heptanoic acid 7-(4-chlorophenyl)-2-(phenylthio)-heptanoic acid 7- (4-chlorophenyl )-2-(4-methylphenylthio)-heptanoic acid 7-(4-chlorophenyl)-2-(phenylsulphinyl)-heptanoic acid 7-(4-chlorophenyl)-2-(4-methylphenylsulphinyl)-heptanoic acid 6- (4-chlo rophenyl) - 2- (4-methylphenyl sulphonyl) -hexanoic acid 7-(4-chlorophenyl)-2-(octylsulphonyl)-heptanoic acid 7-(4-chlorophenyl)-2-(3-chlorophenylsulphonyl)-heptanoic acid 7-(4-chlorophenyl)-2-(4-methoxyphenylsulphonyl)-heptanoic acid 7-(4-chlorophenyl)-2-(3-trifluoromethylphenylsulphonyl)-heptanoic acid 7-(4-chlorophenyl)-2-(4-cyanophenylsulphonyl)-heptanoic acid -26- 7-(4-chlorophenyl)-2- (4-nit rophenyl sulphonyl )-heptanoic acid 7- (4-chlorophenyl )-2- (4- dimethyl aminophenyl sulphonyl )-heptanoic acid 7-(4-chlorophenyl)-2-(4-hydroxyphenylsulphonyl)-heptanoic acid 7-(4-chlorophenyl)-2-(4-acetylphenylsulphonyl)-heptanoic acid 7-(4-chlorophenyl)-2-(2-phenylethylsulphonyl)-heptanoic acid 7-(4-chlorophenyl)-2-(2-phenylethenylsulphonyl)-heptanoic acid 7-(4-chlorophenyl)-2-[5-(4-chlorophenyl)-pentyl-sulphonyl]-heptanoic acid 7-(4-chlorophenyl)-2-(naphth-l-ylsulphonyl)-heptanoic acid 7- (4-chlorophenyl) - 2- (naphth- 2-yl sulphonyl) -heptanoic acid 9- (4-chlorophenyl) - 2- (4-methylphenyl sulphonyl) -nonanoic acid 10-(4-chlorophenyl)-2-(4-methylphenylsulphonyl)-decanoic acid 7— (4-chlorophenoxy) - 2- (4-methylphenyl sulphonyl) -heptanoic acid 7- (4-methoxyphenyl) - 2- (phenyl sulphonyl) -heptanoic acid 7- (4-methoxyphenyl) - 2- (4-methylphenyl sulphonyl) -heptanoic acid -27- 2-(4-chlorophenylsulphonyl)-7-(4-methoxyphenyl)-heptanoic acid 7-(4-methoxyphenyl)-2-(4-methoxyphenylsulphonyl)-heptanoic acid 2-(phenylsulphonyl)-7-(3-trifluoromethylphenyl)-heptanoic acid 2-(4-methylphenylsulphonyl)-7-(3-trifluoromethylphenyl) heptanoic acid 2-(4-chlorophenylsulphonyl)-7-(3-trifluoromethylphenyl) heptanoic acid 2-(4-raethoxyphenylsulphonyl)-7-(3-trifluoromethylphenyl) -heptanoic acid 7- (3,4-dichlorophenyl )-2-(phenyl sulphonyl)-heptanoic acid 7-(3,4-dichlorophenyl)-2-(4-methylphenylsulphonyl) -heptanoic acid 2-(4-chlorophenylsulphonyl)-7-(3,4-dichlorophenyl)-heptanoic acid 7- (3,4-dichlorophenyl) - 2- (4-methoxyphenyl sulphonyl) -heptanoic acid 2-(4-methylphenylsulphonyl)-7-(naphth-l-yl)-heptanoic acid 2- (4-methylphenyl sulphonyl )-7- (naphth-2-yl)-heptanoic acid. The following Examples are given for the purpose of illustrating the present invention:- -28- Example 1. 7- (4-Chlorophenyl )-2- (4-methylphenyl sulphonyl)-heptanoic acid. a) 9.69 g. (40 mMole) ethyl (4-methylphenyl)-sulphonylacetate are added at 50°C., while stirring, to a solution of 40 mMole sodium ethylate in 55 ml. anhydrous ethanol. A suspension is formed which is mixed dropwise, while heating to reflux temperature, with 10.46 g. (40 mMole) 5-( 4-chlorophenyl )-pentyl bromide. The precipitate thereby gradually goes into solution. The reaction mixture is further stirred at reflux temperature, new crystals thereby gradually separating out. After 5 hours, the reaction mixture is evaporated, the residue is mixed with ice water and the mixture is then extracted several times with ethyl acetate. The combined organic phases are dried over anhydrous sodium sulphate, evaporated and the residue chromatographed on silica gel with a mixture of chloroform and toluene (2:1 v/v). There are obtained 15.7 g. (93% of theory) ethyl 7-(4-chlorophenyl)-2-(4-methylphenyl sulphonyl )-heptanoate in the form of a colourless oil. b) A mixture of 4.2 g. (9.9 mMole) of the above ethyl ester, 20 ml.IN aqueous potassium hydroxide solution and 125 ml. methanol is maintained for 2 hours at 40°C. and then 20 ml. IN hydrochloric acid are added thereto. Subsequently, the methanol is evaporated -29- off in a vacuum and the aqueous residue is extracted several times with methylene chloride. The combined organic extracts are dried over anhydrous sodium sulphate and evaporated. There are obtained 3.05 g. (78% of theory) 7-(4-chlorophenyl)-2-(4-methylphenyl-sulphonyl)-heptanoic acid in the form of a colourless oil. The sodium salt is prepared by reaction with a stoichiometric amount of aqueous sodium hydrogen carbonate solution and evaporation of the solution obtained. The amorphous product has a melting point of 90 - 100°C. Analogously to a) and b), there is obtained from ethyl (4-methylphenyl) - sulphonyl acetate and: 3- (4-chlo rophenyl) -propyl bromide: a 1) ethyl 5-(4-chlorophenyl)-2-(4-methylphenyl-sulphonyl)-pentanoate, colourless oil, yield 87% of theory; b 1) 5-(4-chlorophenyl)-2-(4-methylphenylsulphonyl)-pentanoic acid, sodium salt: m.p. 130°C. (decomp.); yield 63% of theory 4-chlorocinnamyl chloride: a 2) ethyl 5- (4-chlorophenyl) - 2- (4-methylphenyl-sulphonyl)-pent-4-enoate; m.p. 87-88°C.; yield 46% of theory; b 2) 5- (4-chlorophenyl) - 2- (4-methylphenyl sulphonyl) -pent-4-enoic acid; m.p. 162-164°C.; yield 82% of theory -30- 4- (4-chlorophenoxy)-butyl bromide: a 3) ethyl 6-(4-chlorophenoxy)-2-(4-methylphenyl-sulphonyl)-hexanoate; colourless oil; yield 67% of theory; b 3) 6-(4-chlorophenoxy)-2-(4-methylphenylsulphonyl)-hexanoic acid, sodium salt m.p. 168-171°C.; yield 82% of theory 6- (4-chlorophenyl) -hexyl bromide: a 4) ethyl 8- (4-chlorophenyl) -2- (4-me thylphenyl-sulphonyl)-octanoate; colourless oil; yield 76% of theory; b 4) 8- (4-chlorophenyl) - 2- (4-me thylphenyl sulphonyl) -octanoic acid; colourless oil; yield 70% of theory 5-phenylpentyl bromide: a 5) ethyl 5-phenyl-2-(4-methylphenyl sulphonyl) -heptanoate; colourless oil; yield 75% of theory; b 5) 5-phenyl- 2- (4-me thylphenyl sulphonyl) -heptanoic acid; colourless oil; yield 63% of theory. Example 2. Ethyl 7-(4-chlorophenyl)-2-(4-methylphenyl-sulphonvloxy) -heptanoate. a) A solution of 11.25 g. (44 mMole) 7-(4-chlorophenyl )-2-oxoheptanoic acid in 175 ml. ethanol is rapidly mixed at 50°C., while stirring, with a solution of 1.84 g. (48.6 mMole) sodium borohydride in 175 ml. ethanol. The reaction mixture is then left to stand for 3 hours at ambient temperature, then evaporated -31- and the residue taken up in water. After acidification, the aqueous phase is extracted with ethyl acetate and the organic extracts are dried and evaporated. The oil remaining behind is dissolved in aqueous sodium hydrogen carbonate solution, the solution is clarified with charcoal and the oil which separates out after acidification is taken up in diethyl ether. The ethereal solution is dried and evaporated to give 7.4 g. (65% of theory) 7-(4-chlorophenyl)-2-hydroxy-heptanoic acid; m.p. 78 - 81°C. b) A mixture of 5.2 g. (20.3 mMole) of the above-obtained a-hydroxycarboxylic acid, 1 g. Amberlite IR 120 (acid form) and 50 ml. anhydrous ethanol is heated for 25 hours at reflux temperature, while stirring. The ion exchanger resin is then filtered off with suction and the filtrate is evaporated. There are obtained 5.7 g. (quantitative yield) ethyl 7-(4-chlorophenyl)-2-hydroxyheptanoate in the form of a colourless oil. c) A solution of 10.0 g. (35.1 mMole) of the above ethyl ester in 70 ml. anhydrous pyridine is mixed portionwise, while stirring at 0°C., with 13.4 g. (70.2 mMole) ]D-toluenesulphonyl chloride within the course of 40 minutes. Subsequently, the mixture is left to stand overnight under cool conditions, then poured on to ice and the aqueous phase is extracted several times with ethyl acetate. The combined ethyl -32- acetate extracts are washed three times with IN hydrochloric acid, dried and evaporated. There are obtained 13.0 g. (84% of theory) ethyl 7-(4-chlorophenyl)-2-(4-methylphenylsulphonyloxy)-heptanoate; colourless oil. Analogously to c), from ethyl 7-(4-chlorophenyl)-2-hydroxyheptanpate, there are prepared the following compounds: c 1) with methanesulphonyl chloride: ethyl 7-(4-chlorophenyl)-2-(methylsulphonyloxy)- heptanoate; colourless oil; yield 80% of theory c 2) with benzene sulphonyl chloride: ethyl 7-(4-chlorophenyl)-2-(phenylsulphonyloxy)- heptanoate; colourless oil; yield 62% of theory c 3) with 4-chlorobenzenesulphonyl chloride: 7-(4-chlorophenyl)-2-[ (4-chlorophenyl)-sulphonyloxy]- heptanoate; colourless oil; yield 67% of theory. Example 3. Ethyl 7-(4-chlorophenyl )-2-methyl-2-f (4-methylphenyl )-sulphonyloxy1-heptanoate. a) 29.3 mMole of a freshly prepared solution of methyl magnesium iodide in diethyl ether are added dropwise to a solution of 8.3 g. (29.3 mMole) ethyl 7-(4-chlorophenyl)-2-oxoheptanoate in 60 ml. anhydrous diethyl ether, while stirring and cooling with ice. The cooling bath is then removed and the mixture subsequently stirred for 2 hours at ambient temperature Subsequently, the reaction mixture is decomposed with -33- an aqueous solution of sodium chloride and the organic phase is separated off, dried and evaporated. There are obtained 7.05 g. (80% of theory) ethyl 7-(4-chlorophenyl)-2-hydroxy-2-methylheptanoate; colourless oil. b) 9.42 g. (47.2 mMole) £-toluenesulphonyl chloride are added portionwise at 0°C., while stirring, to a solution of 7.05 g. (23.6 mMole) of the above-obtained 2-hydroxycarboxylic acid ethyl ester in 100 ml. anhydrous pyridine and the reaction mixture then left to stand overnight in the cold. It is then poured on to ice, extracted with ethyl acetate and the combined extracts are washed three times with IN hydrochloric acid. Subsequently, the solution is dried and evaporated. The residue is chromatographed on silica gel with a mixture of toluene and chloroform (1:1 v/v). There are obtained 6.0 g. (54% of theory) ethyl 7-(4-chlorophenyl )-2-methyl-2-[ (4-methylphenyl)-sulphonyloxy] heptanoate in the form of a colourless oil. Example 4. 7- (4-Chlorophenyl )-2-f (4-methylphenyl)-sulphonyl-amino 1-heptanoic acid. a) A solution of 2.46 g. (107 mMole) sodium in 100 ml anhydrous ethanol is mixed with 17.6 g. (103 mMole) ethyl acetamidocyanoacetate and 25.5 g. (97.5 mMole) 5-(4-chlorophenyl )-pentyl bromide and the mixture is heated under reflux temperature for 6 hours, while -34- stirring. Subsequently, the ethanol is evaporated off, the residue is taken up in water and the pH adjusted to 5 by the addition of a little hydrochloric acid. The mixture is then extracted with ethyl acetate and 5 the combined extracts are dried over anhydrous sodium sulphate and evaporated. The residue is taken up in a little diethyl ether and brought to crystallisation by cooling. There are obtained 16.0 g. (47% of theory) ethyl 2-acetamido-7-(4-chlorophenyl)-2-cyanoheptanoate; 10 m.p. 73 - 77°C. b) A mixture of 16.0 g. (45.6 mMole) of the above-obtained ethyl ester, 16 g. sodium hydroxide and 160 ml. water is heated under reflux temperature for 22 hours, while stirring. The pH is then adjusted to 15 6 with 6N hydrochloric acid and the precipitated crystals are filtered off with suction in the cold. There are obtained 11.3 g. (97% of theory) 7-(4-chlorophenyl )-2-aminoheptanoic acid; m.p. 218 - 220°C. c) A mixture of 11.9 g. (46.5 mMole) of the above-20 obtained amino acid and 120 ml. anhydrous ethanol are saturated with hydrogen chloride while cooling with ice and then left to stand overnight at ambient temperature. The reaction mixture is clarified with charcoal and the solution evaporated. The residue is 25 treated with diethyl ether and the resultant crystals are filtered off with suction in the cold. There are obtained 8.6 g. (58% of theory) ethyl 7-(4-chlorophenyl) 2-aminoheptanoate hydrochloride; m.p. 101 - 102°C. d) 2.85 g. (14.9 mMole) 4-Toluenesulphonic acid chloride are introduced portion-wise, while stirring at 0°C., into a solution of 4.35 g. (13.6 mMole) of the 5 above-obtained amino acid ester in 45 ml. anhydrous pyridine. Stirring is continued for a further 3 hours, with ice cooling, and the reaction mixture is then poured on to ice and acidified with concentrated hydrochloric acid. The aqueous phase is extracted with 10 diethyl ether and the ethereal extracts are washed twice with 0.5N hydrochloric acid. The solution is then dried, decolorised with charcoal and evaporated. The residue is brought to crystallisation by trituration with ligroin. There are obtained 3.6 g. (60% of 15 theory) ethyl 7- (4-chlorophenyl)- 2-[ (4-methylphenyl) -sulphonyl amino] -heptanoate; m.p. 56 - 58°C. e) A mixture of 4.0 g. (9.1 mMole) of the above-obtained sulphonated amino acid ester, 23 ml. IN aqueous potassium hydroxide solution and 55 ml. methanol 20 is stirred for 6 hours at 40°C. The solution is then clarified with charcoal, acidified with 23 ml. IN hydrochloric acid, diluted with water and the oil which separates is taken up in ethyl acetate. The ethyl acetate solution is dried and evaporated. The 25 residue is brought to crystallisation by trituration with ligroin. There are obtained 2.6 g. (70% of theory) 7-(4-chlorophenyl)-2-[(4-methylphenyl)- sulphonylaminoj-heptanoic acid; m.p. 88 - 90°C. Analogously to d) and e), from ethyl 7-(4-chlorophenyl)-2-aminoheptanoate hydrochloride and methanesulphonyl chloride, there are prepared the following compounds: d 1) ethyl 7-(4-chlorophenyl)-2-(methylsulphonyl-amino)-heptanoate; m.p. 60 - 62°C.; yield 68% of theory el) 7- (4-chlorophenyl )-2- (methyl sulphonylamino)-heptanoic acid; m.p. 73 - 75°C.; yield 82% of theory. Example 5. Ethyl 7- (4-chlo rophenyl )-2- (4-chlorophenyl sulphonyl)-heptanoate. In the manner described in Example la), from 40 mMole sodium ethylate, 10.51 g. (40 mMole) ethyl (4-chlorophenyl)-sulphonylacetate and 10.46 g. (40 mMole) 5-(4-chlorophenyl)-pentyl bromide in 100 ml. anhydrous ethanol, there are obtained 9.3 g. (52% of theory) ethyl 7-(4-chlorophenyl)-2-(4-chlorophenyl-sulphonyl)-heptanoate; colourless oil. In analogous manner, there are obtained from 5-(4-chlorophenyl)-pentyl bromide and a) ethyl trifluoromethylsulphonylacetate: ethyl 5-(4-chlorophenyl)-2-(trifluoromethylsulphonyl)-heptanoate; colourless oil; yield 56% of theory b) ethyl methylsulphonylacetate: ethyl 5-(4-chlorophenyl)-2-(methylsulphonyl)-heptanoate; -37- m jp. 60 - 62°C.r yield 64% of theory c) ethyl phenylsulphonylacetate: ethyl 5- (4-chlorophenyl) - 2- (phenyl sulphonyl) -heptanoate; colourless oil: yield 77% of theory d) ethyl 2- (4-methylphenyl sulphonyl) -propionate: ethyl 5- (4-chlorophenyl) -2-methyl-2- (4-methylphenyl-sulphonyl)-heptanoate; colourless oil; yield 74% of theory. Example 6. 7- (4-Chi o rophenyl )-2- (4-chlo rophenyl sulphonyl )-heptanoic acid. In the manner described in Example 1 b), from 6.9 g. (15.6 mMole) ethyl 7-(4-chlorophenyl)-2-(4-chlorophenylsulphonyl)-heptanoate (see Example 5) and 34 ml. IN aqueous potassium hydroxide solution in 100 ml. methanol/ there are obtained 5.1 g. (75% of theory) of the sodium salt of 7- (4-chlorophenyl)-2- (4-chlorophenyl-sulphonyl)-heptanoic acid in the form of an amorphous powder. In an analogous manner, there are obtained from: a) ethyl 7-(4-chlorophenyl)-2-(methylsulphonyl)-heptanoate (see Example 5 b)): 7-(4-chlorophenyl )-2-(methylsulphonyl)-heptanoic acid; m.p. 81 - 84°C.; yield 85% of theory b) ethyl 7- (4-chlorophenyl) - 2- (phenyl sulphonyl) -heptanoate (see Example 5 c)): 7- (4-chlorophenyl)- 2- (phenyl sulphonyl) -heptanoic acid; m.p. 95 - 97°C.; yield 71% of theory c) ethyl 7- (4-chlorophenyl) -2-methyl- 2- (4-methylphenyl sulphonyl)-heptanoate (see Example 5 d)): 7- (4-chlorophenyl) - 2-methyl- 2- (4-methylphenyl-sulphonyl)-heptanoic acid; colourless oil; yield 62% of theory. Example 7. Ethyl 5-(4-chlorophenyl)-2-f3-(4-chlorophenyl)-prop-2-enyl 1-2-(4-methylphenylsulphonyl)-pentan-4-oate. A solution of 40 mMole sodium ethylate in 100 ml. anhydrous ethanol is mixed at 60°C., while stirring, with 4.35 g. (20 mMole) ethyl (4-methylphenyl)-sulphonylacetate. The reaction mixture is allowed to react for 15 minutes and the resultant precipitate is then mixed with 7.48 g. (40 mMole) 4-chlorocinnamyl chloride. The reaction mixture is subsequently heated to the reflux temperature for 5 hours, evaporated and the residue treated with diethyl ether. The ethereal solution is washed with water, dried and evaporated. The residue is chromatographed on silica gel with toluene. There are obtained 13.4 g. (62% of theory) of the title compound; m.p. 75 - 78°C. Example 8. 7-(4-Chlorophenyl)-2-(4-methylphenylsulphonyl )-heptane nitrile. A mixture of 4.5 g. (17.2 mMole) 5-(4-chlorophenyl ) -pentyl bromide, 3.36 g. (17.2 mMole) (4-methyl-phenyl)-sulphonylacetonitrile, 2.26 g. (17.2 mMole) -39- l,8-diazabicyclo(5,4,0)-undec-7-ene and 30 ml. benzene is stirred for 6 hours at ambient temperature. The reaction mixture is then washed with water and the organic phase is dried and evaporated. The residue is chromatographed on silica gel with a mixture of toluene and dioxan (10:1 v/v). There are obtained 4.2 g. (65% of theory) of the title compound in the form of a colourless oil. Example 9. 7- (4-Chlorophenvl )-2- (4-rnethylphenoxy)-heptanoic acid. a) A solution of 63.4 g. (0.186 mole) ethyl 7-(4-chlorophenyl)-2-ethoxycarbonylheptanoate in 500 ml. anhydrous tetrahydrofuran is mixed portionwise with 8.1 g. (0.186 mole) 55% sodium hydride in mineral oil suspension and, for completion of the salt formation, stirring is carried out for 15 minutes. 33.1 g. (0.186 mole) N-bromosuccinimide are then added thereto and the reaction mixture is stirred for 8 hours at ambient temperature. Thereafter, it is poured into water, acidified and extracted with diethyl ether. The combined extracts are washed, dried and evaporated. The residue is chromatographed on silica gel with toluene. There are obtained 61.3 g. (78% of theory) ethyl 2-bromo-7-(4-chlorophenyl)-2-ethoxycarbonyl-heptanoate in the form of a colourless oil. b) A mixture of 102.7 g. (0.245 mole) ethyl 2-bromo-7-(4-chlorophenyl)-2-ethoxycarbonylheptanoate, 367 ml. 2.1683 -40- acetic acid and 367 ml. 6N hydrobromic acid is heated to reflux temperature for 60 hours. The reaction mixture is then diluted with water and extracted with i diethyl ether. The extracts are clarified with char-5 coal, dried and evaporated. The evaporation residue is triturated with ligroin. There are obtained 67.8 g. (86% of theory) 2-bromo-7-(4-chlorophenyl)-heptanoic acidr m.p. 77 - 79°C. c) A solution of 0.16 mole diazomethane in 10: 300 ml. anhydrous diethyl ether is added dropwise at ambient temperature, while stirring, to a solution of 31.0 g. (0.097 mole) 2-bromo-7-(4-chlorophenyl)-heptanoic acid in 250 ml. anhydrous diethyl ether which contains 0.5 ml. methanol until the evolution 15 of nitrogen ceases. The reaction mixture is then evaporated and the residue is chromatographed on silica gel with toluene. There are obtained 18.1 g. (56% of theory) methyl 2-bromo-7-( 4-chlorophenyl)-heptanoate in the form of a colourless oil. 20 d) A mixture of 5.6 g. (17 mMole) methyl 2-bromo-7-(4-chlorophenyl)-heptanoate, 1.82 g. (17 mMole) £-cresol, 7.0 g. (50 mMole) potassium carbonate and 70 ml. butanone is heated to reflux temperature for 36 hours. The inorganic precipitate is then filtered 25 off with suction and the filtrate is evaporated. The residue is taken up in diethyl ether and the solution is washed twice with 0.5N aqueous sodium hydroxide ~— i (ST1* < ■5 -- i V.-- 'w; -41- solution, dried and evaporated. The oil which remains behind is chromatographed on silica gel with toluene. There are obtained 5.3 g. (86% of theory);-methyl 7-(4-chlorophenyl)-2-(4-methylphenoxy)-heptanoate in the form of a colourless oil. e)- A mixture of 3.25 g. (9 mMole) methyl 7-(4-chlorophenyl)-2-(4-methylphenoxy)-heptanoate, 15 ml. IN aqueous potassium hydroxide solution and 45 ml. methanol is heated to 40°C. for 3 hours, while stirring. f The methanol is then evaporated off in a vacuum and the aqueous solution is washed with diethyl ether and j f acidified with dilute hydrochloric acid. The oil which separates out is taken up in diethyl ether and the ethereal solution is dried and evaporated. The residue is triturated with ligroin. There are obtained 2.7 g. (86% of theory) 7-(4-chlorophenyl)-2-(4-methylphenoxy)-heptanoic acid; m.p. 74 - 76°C. Example 10. Methyl 7-(4-chlorophenyl)-2-(4-methylphenylthio)-heptanoate. In the manner described in Example 9 d), from 6.0 g. (18 mMole) methyl 2-bromo-7-(4-chlorophenyl)-heptanoate, 2.23 g. (18 mMole) £-thiocresol, 7.4 g. (54 mMole) potassium carbonate and 75 ml. butanone, there are obtained 3.7 g. (54% of theory) methyl 7-(4-chlorophenyl)-2-(4-methylphenylthio)-heptanoate in the form of a colourless oil. -42- Example 11. 7- ( 4-Chlorophenyl )-2- (4-methylphenyl thio) -heptanoic acid. A solution of 3.27 g. (26.3 mMole) p-thiocresol in 50 ml. ethanol is mixed under an atmosphere of nitrogen at 0°C. with a solution of 2.12 g. (53 mMole) sodium hydroxide in 5 ml. water and then stirred for 10 minutes. A solution of 8.4 g. (26.3 mMole) 2-bromo-7_(4-chlorophenyl)-heptanoic acid in 5 ml. ethanol is then added thereto and the cooling bath is removed. Subsequently, stirring is continued for 6 hours at ambient temperature, whereafter the reaction mixture is left to stand overnight and then evaporated. The residue is taken up in water, washed with diethyl ether and acidified with hydrochloric acid. The oil which separates out is extracted with methylene chloride and the extracts are dried and evaporated. The residue is chromatographed on silica gel with a mixture of toluene and dioxan (5:1 v/v). There are obtained 6.6 g. (69% of theory) 7-(4-chlorophenyl)-2-(4-methy lphenyl-thio)-heptanoic acid; m.p. 58 - 61°C. Example 12. Ethyl 7- (4-chlorophenyl)-2- (4-methylphenyl sulphinyl )-heptanoate. A solution of 8.5 g. (37.6 mMole) ethyl 4-methylphenyl sulphinylacetate in 75 ml. dimethyl sulphoxide is first mixed with 1.64 g. (37.6 mMole) sodium hydride in o © sO 21683 w -43- 55% mineral oil suspension and then with 9.8 g. (37.6 mMole) .5-(4-chlorophenyl)-pentyl bromide. The mixture is subsequently stirred for 4 hours at ambient temperature. It is then poured into water, extracted with 5 diethyl ether and the extracts are washed with water, dried and evaporated. The residue is chromatographed on silica gel with a mixture of n-heptane and butanone (2:1 v/v). There are obtained 8.0 g. (52% of theory) ethyl 7-(4-chlorophenyl)-2-(4-methylphenylsulphinyl)-10 heptanoate in the form of a colourless oil. Example 13. Ethyl 2-(4-methylphenylsulphonyl)-octanoate. In the manner described in Example la), from 40 mMole sodium ethylate, 9.7 g. (40 mMole) ethyl (4-15 methylphenyl)-sulphonylacetate and 7.26 g. (44 mMole) n-hexyl bromide in 100 ml. ethanol, there are obtained 7.3 g. (56% of theory) ethyl 2-(4-methylphenylsulphonyl)-octanoate in the form of a colourless oil. In an analogous manner, there are obtained from 20 ethyl (4-methylphenyl)-sulphonylacetate and a) n-octyl bromide ethyl 2-(4-methylphenylsulphonyl)-decanoate; colourless oil; yield 52% of theory. The methyl ester of the parent acid has already 25 been described (see Ono et al., Bull. Chem. Soc. Japan, 52, 1716/1973). v> A-- • ' ' '.v-"- : - '" •\ . , „ ^...,- -44- 21683 b) n-decyl bromide ethyl ■ 2-(4-methylphenylsulphonyl)-dodecanoate: colourless oil; yield 57% of theory c) n-tetradecyl bromide: 5 ethyl 2-(4-methylphenylsulphonyl)-hexadecanoate; m.p. 38 - 40°C.; yield 68% of theory. © The methyl ester of the parent acid has already been described^ 10 Example 14. 2-(4-Methylphenylsulphonyl)-octanoic acid. In the manner described in Example 1 b), from 4.75 g. (14.5 mMole) ethyl 2-(4-methylphenylsulphonyl)-octanoate (see Example 13) and 32 ml. IN aqueous 15 potassium hydroxide solution in 100 ml. methanol, there are obtained 2.6 g. (60% of theory) 2-(4-methylphenyl-Q sulphonyl)-octanoic acid: m.p. Ill - 123°C., after recrystallisation from ethyl acetate. In an analogous manner, there are obtained from: 20 a) ethyl 2-(4-methylphenylsulphonyl)-decanoate (see Example 13 a)) 2-(4-methylphenylsulphonyl)-decanoic acid; m.p. 116 -118°C.; yield 77% of theory b) ethyl 2-(4-methylphenylsulphonyl)-dodecanoate (see 25 Example 13 b)) 2-(4-methylphenylsulphonyl)-dodecanoic acid; m.p. 71 -73°C., after recrystallisation from ligroin; yield__92% of theory -45- This compound has already been described as a potential tuberculostatic (see Takur and Nargund, Indian J. Chem., Sect. B, 15 B, 287/1977) c) ethyl 2-(4-me thylphenyl sulphonyl)-hexadecanoate (see Example 13 c)) 2-(4-methylphenylsulphonyl)-hexadecanoic acid; m.p. 87 - 90°C.; yield 93% of theory. Example 15. 2-(4-Methylsulphonyl)-4-methyl-5-phenylpent-4-enoic acid. In the manner described in Example 1 a), from 9.69 g. (40 mMole) ethyl (4-methylphenyl)-sulphonyl-acetate, 40 mMole sodium ethylate and 6.66 g. (40 mMole) 2-methyl-3-phenylpent-2-enyl chloride in 100 ml. anhydrous ethanol, there are obtained 8.2 g. (55% of theory) ethyl 2-(4-methylphenylsulphonyl)-4-methyl-5-phenylpent-4-enoate (m.p. 123 - 124°C., recrystallised from ethyl acetate/ligroin) and from this, in the manner described in Example 1 b), 6.8 g. (90% of theory) 2- (4-methylphenyl sulphonyl) -4-methyl-5-phenylpent-4-enoic acid in the form of sticky crystals. The sodium salt melts at 140 - 142°C. In an analogous manner, there are obtained from a) ethyl (4-methylphenyl)-sulphonylacetate and 5-phenyl-pent-4-enyl bromide ethyl 2- (4-methyIphenylsulphonyl)-7-phenylhept-6-enoate; m.p. 46 - 49°C.; yield 56% of theory -46- and from this 2-(4-methylphenylsulphonyl)-7-phenylhept-6-enoic acid; colourless oil; yield 75% of theory; sodium salt: m.p. 144°C. (decomp.) b) ethyl (4-methylphenylsulphonyl)-acetate and 5-(4-methylphenyl)-pentyl bromide ethyl 2-(4-methylphenylsulphonyl)-7-(4-methylphenyl)-heptanoate; colourless oil; yield 67% of theory and from this 2-(4-methyIphenylsulphonyl)-7-(4—methyl-phenyl)-heptanoic acid; colourless oil; yield 83% of theory c) ethyl (4-methyIphenylsulphonyl)-acetate and 4-(4-chlorophenyl)-2-(4-methylphenylsulphonyl)-hexanoate; colourless oil; yield 74% of theory and from this 6-(4-chlorophenyl)-2-(4-methyIphenylsulphonyl )-hexanoic acid; colourless oil; yield 99% of theory; sodium salt: m.p. 143 - 145°C. d) ethyl (3-chlorophenyl)-sulphonylacetate and 4-(4-chlorophenyl)-pentyl bromide ethyl 7-(4-chlorophenyl)-2-(3-chlorophenylsulphonyl)-heptanoate; colourless oil; yield 69% of theory and from this 7-(4-chlorophenyl)-2-(3-chlorophenyl-sulphonyl)-heptanoic acid; m.p. 104 - 106°C.; yield 73% of theory e) ethyl (4-methoxyphenyl )-sulphonylacetate and 5-(4-chl o rophenyl) -pentyl b romi de ethyl 7- (4-chlorophenyl) - 2- (4-methoxyphenyl sulphonyl) -heptanoate; colourless oil; yield 79% of theory -47- and from this 7-(4-chlorophenyl)-2-(4-methoxyphenyl-sulphonyl)-heptanoic acid; m.p. 58 - 65°C.; yield 64% of theory f) ethyl (3-trifluoromethylphenyl)-sulphonylacetate and 5-(4-chlorophenyl)-pentyl bromide ethyl 7- (4-chlorophenyl)—2— (3-trifluoromethyIphenylsulphonyl)-heptanoate; colourless oil; yield 52% of theory and from this 7-(4-chlorophenyl)-2-(3-trifluoromethylphenyl sulphonyl ) -heptanoic acid; m.p. 107 - 108°C.; yield 73% of theory; sodium salt: m.p. 147 - 150°C. g) ethyl (4-cyanophenyl)-sulphonylacetate and 5-(4-chlorophenyl)-pentyl bromide ethyl 7- (4-chlorophenyl )-2- (4-cyanophenyl sulphonyl )-heptanoic acid; colourless oil; yield 65% of theory h) ethyl (4-acetylphenyl)-sulphonylacetate and 5-(4-chlo rophenyl) -pentyl bromi de ethyl 2- (4-acetylphenyl sulphonyl ).-7- (4-chlorophenyl) -heptanoate; colourless oil; yield 54% of theory i) ethyl (l-naphthyl)-sulphonylacetate and 5-(4-chlorophenyl)-pentyl bromide ethyl 7- (4-chlorophenyl )-2-[ (1-naphthyl)-sulphonyl]-heptanoate; colourless oil; yield 71% of theory and from this 7-(4-chlorophenyl)-2-[(1-naphthyl)-sulphonyl]-heptanoic acid; colourless oil; yield 63% of theory; sodium salt: m.p. 168 - 170°C. -43- j) ethyl (4-methylphenyl)-sulphonyl acetate and 6-(4-chl o rophenyl) -hexy 1 bromi de ethyl 8- (4-chlorophenyl) -2- (4-methylphenyl sulphonyl) -octanoate; colourless oil; yield 67% of theory and from this 8-(4-chlorophenyl )-2-( 4-methy Iphenylsulphonyl )-octanoic acid; colourless oil; yield 71% of theory k) ethyl (4-methylphenyl)-sulphonylacetate and 4-(4-chlorophenoxy)-butyl bromide ethyl 6-(4-chlorophenoxy)-2-(4-methylphenylsulphonyl)-hexanoate; colourless oil; yield 67% of theory and from this 6- (4-chlorophenoxy )-2- (4-methy Iphenylsulphonyl >-hexanoic acid; colourless oil; yield 82% of theory; sodium salt: m.p. 168 - 171°C. 1) ethyl (4-methylphenyl )-sulphonylacetate and 5-(4-chlorophenoxy)-pentyl bromide ethyl 7-(4-chlorophenoxy)-2-(4-methylphenylsulphonyl)-heptanoate; m.p. 86 - 89°C.; yield 63% of theory and from this 7-(4-chlorophenoxy)-2-(4-methy Iphenylsulphonyl)-heptanoic acid; m.p. 88 - 90°C.; yield 87% of theory m) ethyl (4-methylphenyl )-sulphonylacetate and 5-(4-methoxyphenyl)-pentyl bromide ethyl 7- (4-methoxyphenyl) -2- (4-methylphenyl sulphonyl)-heptanoate; m.p. 64 - 68°C.; yield 56% of theory and from this 7-(4-methoxyphenyl)-2-(4-methy Iphenylsulphonyl)-heptanoic acid; colourless oil; yield 70% -49- of theory; sodium salt: m.p. 72 - 80°C. (decomp.) n) ethyl (4-methylphenyl)-sulphonyl acetate and 5— ( 3— trifluoromethylphenyl)-pentyl bromide ethyl 2- (4-methylphenyl sulphonyl)-7- ( 3-trifluoromethyl-5 phenyl)-heptanoate; m.p. 56 - 58°C.; yield 53% of theory and from this 2-(4-methyIphenylsulphonyl)-7-(3-tri-fluoromethylphenyl)-heptanoic acid? m.p. 62°C.; yield 87% of theory o) ethyl (4-methylphenyl)-sulphonyl acetate and 5-(2-10 methoxyphenyl) -pentyl bromide ethyl 7- (2-me thoxyphenyl) - 2- (4-methylphenyl sulphonyl) — heptanoate; colourless oil; yield 64% of theory and from this 7- ( 2-methoxyphenyl )-2- (4-methylphenyl )-sulphonyl)-heptanoic acid; colourless oil; yield 70% 15 of theory; sodium salt: m.p. 75 - 76°C. p) ethyl (4-methylphenyl)-sulphonyl acetate and 5-(3-methoxyphenyl)-pentyl bromide ethyl 7- (3-methoxyphenyl) - 2- (4-methylphenyl sulphonyl) -heptanoate; colourless oil; yield 52% of theory 20 and from this 7-(3-methoxyphenyl)-2-(4-methoxyphenyl-sulphonyl)-heptanoic acid; colourless oil; yield 60% of theory; sodium salt: m.p. 84 - 85°C. q) ethyl (4-methylphenyl)-sulphonyl acetate and 3-(4-chl o rophenyl) -p rop- 2-ynyl bromide 25 ethyl 5-(4-chlorophenyl)-2-(4-me thylphenyl sulphonyl)-pent-4-ynoate; m.p. 78 - 79°C.; yield 57% of theory and from this 5-(4-chlorophenyl)-2-(4-methylphenyl- -50- sulphonyl)-pent-4-ynoic acid; m.p. 154 - 157°C.; yield 76% of theory. Example 16. 2-(Aminocarbonyl)-7-(4-chlorophenyl)-heptanoic acid. a) A mixture of 9.0 g. (34.4 mMole) 5-(4-chlorophenyl ) -pentyl bromide, 5.2 g. (34.4 mMole) 1,8-diaza-bicyclo(5,4,0)-undec-7-ene and 18 ml. anhydrous benzene is mixed, while stirring, with a solution of 3.9 g. (34.4 mMole) ethyl cyanoacetate in 36 ml. anhydrous benzene and the mixture further stirred for 16 hours at ambient temperature. The organic phase is then washed -with water, dried and evaporated. The residue is chromatographed on silica gel with a mixture of n-heptane and butanone (2:1 v/v). There are obtained 8.8 g. (87% of theory) ethyl 7-(4-chlorophenyl)-2-cyanoheptanoate in the form of a colourless oil. b) 12 g. (41 mMole) Ethyl 7-(4-chlorophenyl)-2-cyanoheptanoate and 96 g. polyphosphoric acid are heated to 100°C. for 3 hours, while stirring. The reaction mixture is then diluted with 200 ml. water and the mixture is extracted three times with methylene chloride. The combined extracts are washed with water, dried and evaporated. There are obtained 10 g. (78% of theory) ethyl 2-(aminocarbonyl)-7-(4-chlorophenyl)-heptanoate; m.p. 110 - 111°C. c) A mixture of 7.8 g. (25 mMole) ethyl 2-(aminocarbonyl ) -7- (4-chlorophenyl ) -heptanoate, 25 ml. IN aqueous potassium hydroxide solution and 100 ml. methanol is stirred for 4 hours at 40°C. The methanol is then evaporated off and the residue is treated with charcoal and acidified with 2N hydrochloric acid. The separated crude acid is extracted with methylene chloride and the extracts are dried and then evaporated. The residue is recrystallised from a mixture of ethyl acetate and ligroin. There are obtained 4.8 g. (68% of theory) 2-(aminocarbonyl)-7-(4-chlorophenyl)-heptanoic acid; m.p. 125 - 126°C. In an analogous manner, from 3-(4-chlorophenyl)-propyl bromide and ethyl cyanoacetate there is obtained a 1) ethyl 5-(4-chlorophenyl)-2-cyanoacetate; colourless oil; yield 74% of theory b 2) ethyl 2-(aminocarbonyl)—5—(4-chlorophenyl)-pentanoate: m.p. 99 - 101°C., recrystallised from ethyl acetate/ligroin from 6-(4-chlorophenyl)-hexyl bromide and ethyl cyanoacetate there is obtained a 2) ethyl 8-(4-chlorophenyl)-2-cyanooctanoate; colourless oil: yield 87% of theory b 2) ethyl 2-(aminocarbonyl)-8-(4-chlorophenyl)- octanoater m.p. 121 - 122°C., recrystallised from ethyl acetate/ligroin. Example 17. Ethyl 2-acetyl-7-(4-chlorophenyl)-heptanoate. A solution of 6.0 g. (46 mMole) ethyl acetoacetate sjsssbe??.:. *r\ - - -. -V • - J.V O -52- in 6 ml. anhydrous ethanol is added dropwise, while stirring, to a solution of 23 mMole sodium ethylate in 18 ml. ethanol. Stirring is continued for 15 minutes for completion of the salt formation and then 5 a solution of 6.0 g. (23 mMole) 5-(4-chlorophenyl)-pentyl bromide in 6 ml. anhydrous ethanol is added thereto. The mixture is now heated under reflux for 3 hours and subsequently completely evaporated. The residue is mixed with water and the mixture is neutral-10 ised with 2N hydrochloric acid. The organic components are then extracted with diethyl ether and the combined extracts are dried and evaporated. The residue is chromatographed on silica gel with a mixture of n-heptane and butanone. There are obtained 5.8 g. (81% 15 of theory) ethyl 2-acetyl-7-(4-chlorophenyl)-heptanoate in the form of a colourless oil. (3 Example 18. Ethyl 5- (4-chlorophenyl)-2- f 3- (4-chlorophenyl)-prop-2-yn-l-yl1-2-(4-methylphenylsulphonyl)-pent-4-ynoate. 20 In the manner described in Example 1 a), from o 7.8 g. (34 mMole) ethyl (4-methylphenyl)-sulphonyl-acetate, 68 mMole sodium ethylate and 16.5 g. (68 mMole) 4-(4-chlorophenyl)—prop-2-yn-l-yl bromide, there are obtained 8.1 g. (44% of theory) of the tital compound; 25 m.p. 90 - 93°C. Example 19. Ethyl 2-(aminocarbonyl)-7-(4-chlorophenyl)-heptanoate. Sm -53- A saturated solution of gaseous ammonia in 25 ml. methylene chloride is added dropwise at -10°C. to a solution of 5.6 g. (17 mMole) ethyl 2-(chlorocarbonyl)-4-(4-chlorophenyl)-heptanoate in 50 ml. methylene chloride. The reaction mixture is stirred for 30 minutes at ambient temperature, filtered off with suction from ammonium chloride and the filtrate is washed with water, dried and evaporated. The residue is chromatographed on silica gel with a mixture of toluene and dioxan (5:1 v/v). There are obtained 3.6 g. (68% of theory) ethyl 2-(aminocarbonyl)-7-(4-chlorophenyl ) -heptanoate; m.p. 110 - 111°C. Example 20. By appropriate choice of the starting components and of the reaction conditions, the following compounds can be prepared analogously to the preceding Examples: 7-(4-chlo rophenyl)-2-methoxyheptanoic acid 7-(4-chlorophenyl)-2-methylthioheptanoic acid 7-(4-chlorophenyl)-2-methylsulphoxyheptanoic acid 7-(4-chlorophenyl)-2-phenoxyheptanoic acid 7-(4-chlorophenyl)-2-(4-chlorophenoxy)-heptanoic acid 7_ (4-chlorophenyl)-2- (4-methoxyphenoxy)-heptanoic acid 7-(4-chlorophenyl)-2-(3-trifluoromethylphenoxy)-heptanoic acid 7_(4-chlorophenyl)-2-(4-cyanophenoxy)-heptanoic acid 2- (4-methoxyphenoxy) -7-phenylheptanoic acid 7-(4-methoxyphenyl)-2-(4-methylphenoxy)-heptanoic acid -54- 2- (4-methylphenoxy)-7-( 3-trifluoromethylphenyl )-heptanoic acid 7- (4-chlorophenyl )-2-phenylthioheptanoic acid 7- (4-chlorophenyl )-2- (4-chlorophenyl thio)-heptanoic acid 7- (4-chlorophenyl )-2- (4-methoxyphenyl thio) -heptanoic acid 7- (4-chlorophenyl )-2- (3-trifluoromethylphenylthio)-heptanoic acid 7- (4-chlorophenyl)-2- (4-cyanophenylthio)-heptanoic acid 2- (4-methylphenyl)-thio-7-phenylheptanoic acid 7- (4-methoxyphenyl)-2- (4-me thylphenyl thio )-heptanoic acid 2- (4-methylphenyl)-thio-7- (3-trif luoromethylphenyl )-heptanoic acid 7- (4-chlorophenyl)- 2-phenyl sulphinylheptanoic acid 7- (4-chlorophenyl) - 2- (4-chlorophenyl sulphinyl) -heptanoic acid 7- (4-chlorophenyl) - 2- (4-methoxyphenyl sulphinyl) -heptanoic acid 7- (4-chlorophenyl )-2- (3-trif luoromethylphenyl sulphinyl )-heptanoic acid 7- (4-chlorophenyl) - 2- (4-cyanophenyl sulphinyl) -heptanoic acid 2- (4-methylphenyl sulphinyl) -7-phenylheptanoic acid 7- (4-methoxyphenyl) - 2- (4-methylphenyl sulphinyl) -heptanoic acid -55- 2-(4-methylphenyl )-sulphinyl-7- (3-trifluoromethylphenyl) heptanoic acid 6-cyclohexyl-2-(4-methylphenylsulphonyl)-hexanoic acid 8-cyclohexyl-2- (4-methylphenyl sulphonyl)-octanoic acid 8-methoxy-2-(4-methylphenylsulphonyl)-octanoic acid 8-methylthio-2-(4-methylphenylsulphonyl)-octanoic acid 8-methylsulphinyl-2-(4-methylphenylsulphonyl)-octanoic acid 4-methyl- 2- (4-methylphenyl sulphonyl) -5-phenylpentanoic acid 2-(4-methylphenylsulphonyl)-5-phenylpent-4-ynoic acid 2-(4-methylphenylsulphonyl)-6-phenylhexanoic acid 7-phenyl-2-(phenylsulphonyl)-heptanoic acid 2-(4-chlorophenylsulphonyl)-7-phenylheptanoic acid 2-(4-methoxyphenylsulphonyl)-7-phenylheptanoic acid 2-(4-cyanophenylsulphonyl)-7-phenylheptanoic acid 7-phenyl-2-(3-trifluoromethyIphenylsulphonyl)-heptanoic acid 7,7-dimethyl-2-(4-methylphenylsulphonyl)-7-phenyl-heptanoic acid 2-(4-methylphenylsulphonyl)-8-phenyloctanoic acid 6-(4-methylphenyl)-2-(4-methylphenylsulphonyl)-hexanoic acid 8-(4-methylphenyl)-2-(4-methylphenylsulphonyl)-octanoic acid 10-(4-methylphenyl)-2-(4-methylphenylsulphonyl)-decanoic acid 7-(4-chlorophenyl)-2-(octylsulphonyl)-heptanoic acid 7-(4-chlorophenyl)-2-(4-ni trophenylsulphonyl)-heptanoic acid 7-(4-chlorophenyl)-2-(4-dimethylaminophenylsulphonyl)-heptanoic acid 7-(4-chlorophenyl)-2-(4-hydroxyphenylsulphonyl)-heptanoic acid 7-(4-chlorophenyl)-2-(2-naphthylsulphonyl)-heptanoic acid 9-(4-chlorophenyl)-2-(4-methylphenylsulphonyl)-nonanoic acid 10-(4-chlorophenyl)-2-(4-methylphenylsulphonyl)-decanoic acid 7-(4-chlorophenyl)-2-(2-phenylethylsulphonyl)-heptanoic acid 7-(4-chlorophenyl)-2-(2-phenylethenylsulphonyl)-heptanoic acid 7- (4-chlorophenyl.)-2- [ 5- (4-chlorophenyl) -pentyl-sulphonyl]-heptanoic acid 7-(4-chlorophenyl)-2-(4-methylphenylsulphonyl)-hept-6-enoic acid 5-(4-methoxyphenyl)-2-(4-methylphenylsulphonyl)-pent-4-ynoic acid 2-(4-methylphenylsulphonyl)-5-(3-trifluoromethylphenyl)-pent-4-ynoic acid 5_(4-chlorophenyl)-2-(phenylsulphonyl)-pent-4-ynoic acid -57- 5-(4-chlorophenyl)-2-(4-chlorophenylsulphonyl)-pent-4-ynoic acid 5-(4-chlorophenyl)-2-(3-trif luoromethy Iphenylsulphonyl)-pent-4-ynoic acid 5- (4-chlorophenyl) - 2- (4-methoxyphenyl sulphonyl) -pent- 4-ynoic acid 5- (4-chlorophenyl) -2- (4-cyanophenyl sulphonyl) -pent-4-ynoic acid 7-(4-methoxyphenyl )-2- (phenylsulphonyl )-heptanoic acid 2- (4-chlo rophenyl sulphonyl) -7- (4-methoxyphenyl)-heptanoic acid 7- (4-methoxyphenyl )-2- (4-methoxyphenyl sulphonyl)-heptanoic acid 2- (phenyl sulphonyl )-7- (3-trifluoromethylphenyl)-heptanoic acid 2-(4-chlorophenylsulphonyl)-7-(3-trifluoromethylphenyl)-heptanoic acid 2- (4-methoxyphenyl sulphonyl)-7- (3-trifluoromethylphenyl )-heptanoic acid 7-(3,4-dichlorophenyl)-2-(phenylsulphonyl)-heptanoic acid 7- (3,4-dichlorophenyl)-2- (4-methylphenyl sulphonyl )-heptanoic acid 2- (4-chlo rophenyl sulphonyl )-7- (3,4-dichlorophenyl )-heptanoic acid 7-(3,4-dichlorophenyl)-2-(4-methoxyphenylsulphonyl)-heptanoic acid -58- 7-(4-fluorophenyl)-2-(4-methylphenylsulphonyl)-heptanoic acid 7- (3-chlorophenyl)—2— (4-me thylphenyl sulphonyl )-heptanoic acid 5 7- (4-aminophenyl) - 2- (4-methylphenyl sulphonyl) -heptanoi c acid 2 - (4-methylphenyl sulphonyl) -7- (4-nit rophenyl) -heptanoic acid 2- (4-methylphenyl sulphonyl )-7- (1-naphthyl )-heptanoic acid 10 2- (4-methylphenyl sulphonyl )-7- (2-naphthyl)-heptanoic acid 2-acetoxy-7-( 4-chlorophenyl)-heptanoic acid 2-benzoyloxy-7- (4-chlorophenyl) -heptanoic acid 2-amino-7-(4-chlorophenyl)-heptanoic acid 2-amino-8-(4-chlorophenyl)-octanoic acid 15 2-amino-7- (4-methoxyphenyl)-heptanoic acid 2-amino-7- (3-trifluoromethylphenyl)-heptanoic acid 2-acetylamino-7- (4-chlorophenyl )-heptanoic acid 2-(benzoylamino )-7- (4-chlorophenyl)-heptanoic acid 7- (4-chlorophenyl )-2-diethylaminoheptanoic acid 20 7-(4-chlorophenyl)-2-phenylaminoheptanoic acid 2-benzyl ami no-7- (4-chlorophenyl )-heptanoic acid 7- (4-chlorophenyl )-2-piperidinoheptanoic acid 7- (4-chlorophenyl)-2-morpholinoheptanoic acid 7- (4-chlorophenyl) -2- (4-phenylpiperazino)-heptanoic acid 25 2-aminosulphonyl-7-(4-chlorophenyl)-heptanoic acid 7- (4-chlorophenyl) - 2- (diethylaminosulphonyl) -heptanoic acid -59- 7-(4-chlorophenyl)-2-(piperidinosulphonyl)-heptanoic acid 2-aminocarbonyl-5- (4-chlorophenyl )-pent-4-enoic acid 2-aminocarbonyl-7-(4-chlorophenyl)-2-methylheptanoic acid 2-aminocarbonyl-7-phenylheptanoic acid 2-aminocarbonyl-7-(4-methoxyphenyl)-heptanoic acid 2-aminocarbonyl-7-(4-methylphenyl)-heptanoic acid 2-aminocarbonyl-7- (3-trif luoromethylphenyl)-heptanoic acid 7-(4-chlorophenyl)-2-(phenylcarbonyl)-heptanoic acid 7- (4-chlo rojphenyl )-2- (dimethylaminocarbonyl )-heptanoic acid 7-(4-chlorophenyl)-2-(diethylaminocarbonyl)-heptanoic acid 7-(4-chlorophenyl)-2-(phenylaminocarbonyl)-heptanoic acid 2-(benzylaminocarbonyl)-7-(4-chlorophenyl)-heptanoic acid 7-(4-chlorophenyl)-2-(morpholinocarbonyl)-heptanoic acid 7-(4-chlorophenyl)-2-(4-phenylpiperazinocarbonyl)-heptanoic acid 2-(4-benzylpiperazinocarbonyl)-7-(4-chlorophenyl)-heptanoic acid 5-(4-chlorophenyl)-2-cyanopent-4-enoic acid 7-(4-chlorophenyl)-2-cyano-2-methylheptanoic acid 2-cyano-7-pentylheptanoic acid 2-cyano-7-(4-methoxyphenyl)-heptanoic acid 2-cyano-7-(4-methylphenyl)-heptanoic acid 2-cyano-7-(3-trifluoromethylphenyl)-heptanoic acid 7_(4_chlorophenyl)-2-(piperidinocarbonyl)-heptanoic acid. ioO - -fr§—a- : 8-phenyl-2-(phenylsulphonyl)octanoic acid 8-2-10 2- 6-8-10 7-2-7-2-7-7-7-7-7- 7-phenyl-2-(phenoxy)heptanoic acid 2-2-2-2-2-8-10 7- 8-7- 2-2- 4-methoxyphenyl)-2-[4-methylphenyl)sulphonyl]octanoic acid 4-methylphenyl)sulphonyl]-9-phenylnonanoic acid phenyl-2-(phenylsulphonyl)decanoic acid (4-methylphenyl)sulphonyl]-12-phenyldodecanoic acid 2-methoxyphenyl)-2-[(4-methylphenyl)sulphonyl]hexanoic acid 2-methoxyphenyl)-2-[(4-methylphenyl)sulphonyl]octanoic acid (2-methoxyphenyl)-2-[(4-methylphenyl)sulphonyl]decanoic acid 2-methoxyphenyl)-2-(phenylsulphonyl)heptanoic acid (4-chlorophenyl)sulphonyl]-7-(2-methoxyphenyl)heptanoic acid 2-methoxyphenyl)-2-[4-methoxyphenyl)sulphonyl]heptanoic acid (4-cyanophenyl)sulphonyl]-7 -(2-methoxyphenyl)heptanoic acid 5-chloro-2-methoxyphenyl)-2-(phenylsulphonyl)heptanoic acid 5-chloro-2-methoxyphenyl)-2-[(4-methylphenyl)sulphonyllheptanoic acid 5-chloro-2-methoxyphenyl)-2-[(4-cyanophenyl)sulphonyllheptanoic acid 5-fluoro-2-methoxyphenyl)-2-[(4-methylphenyl)sulphonyl]heptanoic acid 5-bromo-2-methoxyphenyl)-2-[(4-methylphenyl)sulphonyllheptanoic acid 4-methoxyphenoxy)-7-phenylheptanoic acid 3-trifluoromethylphenoxy)-7-phenylheptanoic acid 4-cyanophenoxy)-7-phenylheptanoic acid 4-methylphenoxy)-8-phenyloctanoic acid 4-methylphenoxy)-10-phenyloctanoic acid 4-chlorophenyl)-2-(4-methylphenoxy)octanoic acid (4-chlorophenyl)-2-(4-methylphenoxy)decanoic acid 2-methoxyphenyl)-2-(4-methylphenoxy)heptanoic acid 2-methoxyphenyl)-2-(4-methylphenoxy)octanoic acid 5-chlor-2-methoxyphenyl)-2-(4-methylphenoxy)heptanoic acid 7-phenyl-2-(phenylthio)heptanoic acid (4-chlorophenyl)thio]-7-phenylheptanoic acid (4-methoxyphenyl)thio]-7-phenylheptanoic acid 7-phenyl-2-[(3-trifluoromethylphenyl)thio]heptanoic acid 2-[(4-cyanophenyl)thio]-7-phenylheptanoic acid 2-[(4-methylphenyl)thio]-8-phenyloctanoic acid 2-[(4-methylphenyl)thio]-10-phenyldecanoic acid 8-(4-chlorophenyl)-2-[(4-methylphenyl)thio]octanoic acid </div>

Claims

<div class="application article clearfix printTableText" id="claims"> 10-(4-chlorophenyl)-2-[4-methylphenyl)thio]decanoic acid 7-(2-methoxyphenyl)-2-[(4-methylphenyl)thiolheptanoic acid 8-(2-methoxyphenyl)-2-[(4-methylphenyl)thio]octanoic acid 7-(5-chloro-2-methoxyphenyl)-2-[(4-methylphenyl)thiolheptanoic acid 5-phenyl-2-(phenylsulphonyl)-pent-4-ynoic acid
2-[(4-chlorophenyl)sulphonyl3-5-phenyl-pent-4-ynoic acid 5-phenyl-2-[(
3-trifluoromethylphenyl)sulphonyl]-pent-4-ynoic acid 2-[(4-methoxyl)sulphonyl]-5-phenyl-pent-4-ynoic acid 2-[(
4-cyanophenyl)sulphonyl]-
5-phenyl-pent-4-ynoic acid 2-[(4-methylphenyl)sulphonyl]-7-phenyl-hept-
6-ynoic acid 5-(2-methoxyphenyl)-2-[(4-methylphenyl)sulphonyl]-pent-4-ynoic acid 5-(5-chloro-2-methoxyphenyl)-2-[(4-methylphenyl)sulphonyl]-pent-4-ynoi acid 7-(4-chlorophenyl)-3.3-dimethyl-2-[(4-methylphenyl)sulphonyllheptanoic acid 8-(4-chlorophenyl)-3.3-dimethyl-2-[(4-methylphenyl)sulphonyl]octanoic acid 10-(4-chlorophenyl)-3.3-dimethyl-2-[(4-methylphenyl)-sulphonyl]decanoi acid 7-(4-chlorophenyl)-3.3-dimethyl-2-[4-methylphenyl)thio]-heptanoic acid 8-(4-chloropheynl)-3.3-dimethyl-2-[(4-methylphenyl)thiol-octanoic acid 10-(4-chlorophenyl)-3.3-dimethyl-2-[(4-methylphenyl)thio]-decanoic aci
7-(4-chlorophenyl)-3.3-dimethyl-2-(4-methylphenoxy)-heptanoic acid
8-(4-chlorophenyl)-3.3-dimethyl-2-(4-methylphenoxy)-octanoic acid 10-(4-chlorophenyl)-3.3-dimethyl-2-(4-methylphenoxy)-decanoic acid 7-phenyl-2-[(2-phenylethyl)sulphonyl]heptanoic acid 2.16830 -ee=- WHAT WE CLAIM IS; 1. Carboxylic acid derivatives of the general formula:- R, - A - C - COOH (I) X I X wherein R, is an aryl or aryloxy radical, unsubstituted or substituted in one or more positions by hydroxy], halogen, lower alkyl. lower alkoxy, trifluoromethyl, cyano. nitro or amino, whereby the amino group can be substituted once or twice by lower alkyl. R2 is a hydrogen atom, a lower alkyl radical having up to -1 carbon atoms or an R,-A- radical wherein Rj has the meaning given above and, when X is a cyano group, R2 can also be an acylamino or amino radical, A is a straight-chained or branched, saturated or unsaturated alkylene radical containing 3 to 8 carbon atoms which has a chain length of at least 3 carbon atoms, and X is a cyano group or a radical of the general formula -B-R^ . or -D-NR^Rg, in which B is 0, S, SO, S02, O(CO), 0S02» NHCO, NHS02 or CO, D is a valency bond, S02 or CO, Rg is an alkyl, trifluoromethyl, cycloalkyl, aralkyl, aralkenyl or aryl radical, the aryl moieties of which are unsubstituted or substituted in one or more positions by hydroxyl. halogen, lower alkyl, lower alkoxy, trifluoromethyl, cyano, nitro or amino, whereby the amino group can be substituted once or twice by lower alkyl, R« is a hydrogen atom, a lower alkyl radical or an unsubstituted or substituted aryl or aralkyl in one or more radical positions by h^roxyl, halogen, lower alkyl, lower alkoxy, trif luoromethyl, cyano, nitro or afoi-no, whereby the amino group can be substituted once or twice by lower alkvl. and R5 is a hydrogen atom or a lower alkyl radical or and Rg together form an alkylene chain containing 4 to 6 carbon atoms which can be interrupted by 0, S or NRC and Rc is a hydrocen atom 21683 -63- • a lower alkyl radical or an unsubstituted or substituted phenyl or benzyl in one or more positions by hydroxyl, halogen, lower alkyl, lower alkoxy, trifluoromethyl, cyano, nitro or amino, whereby the amino group can be substituted once or twice by lower alkyl, as well as the physiologically acceptable salts, esters, amides and nitriles thereof, with the proviso a) when A is an alkylene radical with 3 carbon atoms, al) in all cases, an aryl radical is not an unsubstituted phenyl radical and a2) X is not -CN, -NHCOR3 or —NR^R,.• b) when X is a methyl thio radical, R2 is not a methyl radical; c) when X is -NH2 or -NHCOCH^, R^A- is not 4-phenyl- butyl or 4-(4-methoxyphenyl)-butyl; d) when X is 2,4-dinitrophenyl, R^A- is not 4-phenyl-butyl or 5-phenylpentyl; and e) when X is -COCH^, R^A- is not 3-(2-chlorophenyl)-propyl or 5-(4-methoxyphenyl)-pentyl. 2. Carboxylic acid derivatives according to claim 1, wherein is a phenyl, naphthyl, phenyloxy or naphthyloxy radical^ which can be substituted one or more times by hydroxyl, halogen, alkyl having up to 4 carbon atoms, alkoxy having up to four carbon atoms, trif luoromethyl, cyano, nitro, amino alkylamino or dialkylamino radicals wherein the alkyl moiety or moieties have ud to 4 carbon atoms. R, is a hvdrooren atom, a methvl that: chained, saturated or unsaturated alkj containing 3 to 8 carbon atoms and X is a c\«&io, I 21 65330 D Q 0 O alkoxycarbonyl, alkoxy, alkylsulphenyl, alkylsulphinyl, alkyl sulphonyl, tri f luoromethyl sulphonyl , phenoxy, phenylsulphenyl, phenylsulphinyl, phenylsulphonyl, naphthylsulphonyl, phenylethylenesulphonyl, phenyl-ethenylenesulpfionyl, alkylcarbonyloxy, alkyl sulphonyloxy, alkylcarbonylamino, alkyl sulphonyl amino, alkylcarbonyl, phenylcarbonyloxy, phenyl sulphonyloxy, phenylcarbonyl-amino, phenyl sulphonyl amino, phenylcarbonyl, amino, dialkylamino, phenylamino, benzylamino, morpholino, piperidino, 4-benzylpiperazino, aminosulphonyl, dialkylamino sulphonyl , piperidinosulphonyl, carbamoyl, dialkyl-aminocarbonyl, phenyl ami, nocarbonyl, benzylaminocarbonyl, piperidinocarbonyl, morpholinocarbonyl, 4-phenyl-piperazinocarbonyl or 4-benzylpiperazinocarbonyl radical, the phenyl ring in all cases being optionally substituted by the above-mentioned substituents. 3. A carboxylic acid derivative according to claim 1 substantially as herein'described or exemplified. 4. Process for the preparation of carboxylic acid derivatives of the general formula:- wherein is an aryl or aryloxy radical unsubstituted or substituted in one or more positions by hydroxyl, halogen, lower alkyl, lower alkoxy," trif luoromethyl, cyano, nitro or amino, whereby the amino groS^cSn^be substituted once or twice by lower alkyl, - A - C - COOH (I) X R2 is a hydrogen atom, a lower alkyl radical having 1 to 4 carbon atoms or an R^A- radical wherein R1 has the meaning given above and, when X is a cyano group, Rz can also be an acylamino or amino radical, A is a straight-chained or branched, saturated or unsaturated alkylene radical containing 3 to 8 carbon atoms which has a chain length of at least 3 carbon atoms, and X is a cyano group or a radical of the general formula -B-R3 or -D-NR^Rg, in which B is 0, S, SO, S02, 0(C0), 0S02, NHCO, NHS02 or CO, D is a valency bond, S02 or CO, R3 is an alkyl, trif luoromethyl, cycloalkyl, aralkyl, aralkenyl, or aryl radical, the aryl moieties of which are optionally substituted in one or more positions by hydroxyl, halogen, lower alkyl, lower alkoxy, trif luoromethyl, cyano, nitro or amino, whereby the amino group can be substituted once or twice by lower alkyl, R^ is a hydrogen atom, a lower alkyl radical or an aryl or aralkyl radical, wherein each aryl or aralkyl radical is optionally substituted in one or more radical positions by hydroxyl, halogen, lower alkyl, lower alkoxy, trifluoromethyl, cyano, nitro or amino, whereby the amino group can be substituted once or twice by lower alkyl, and Rg is a hydrogen atom or a lower alkyl radical or R^ and Rj together form an alkylene chain containing 4 to 6 carbon atoms which can be interrupted by 0, S or NR6 and Rfi is a hydrogen atom, a lower alkyl radical or a phenyl or benzyl radical, wherein each phenyl or benzyl radical is optionally substituted in one or more positions by hydroxyl, halogen, lower alkyl, lower alkoxy, trifluoromethyl, cyano, nitro or amino, whereby the amino group can be substituted once or twice by lower alkyl, as well as of the physiologically acceptable salts, esters, amides and nitriles thereof, with the proviso that: a) when A is an alkylene radical with 3 carbon atoms, al) in all cases, an aryl radical R1 is not an unsubstituted phenyl radical and a2) X is not -CN, -NHC0R3 or -NR^; b) when X is a methyl thio radical, R2 is not a me£tiyl radical; 'J ->r-r- ■ 'O-:-: H 66 o o 7' 6820 c. I c) when X is -NH2 or -NHCCCH3, Rj^A- is not 4-phenyl-butyl or 4-(4-methoxyphenyl)-butyl? d) when X is 2,4-dinitrophenyl, Rj_A- is not 4-phenyl-O buty1 or 5-phenylpentyl; and e) when X is -COCH^, R-^A- is not 3- (2-ch.lorophenyl )— propyl or 5-(4-methoxyphenyl)-pentyl, wherein (j) A) a compound of the general formula :- zi I1 H - C - W (II) 1 Z2 in which Z2 is -COOR7, -CN, -CO-R3, -SO-Rg, -S0,-R3# -CONH^ or ~S02NH2, Z2 is a hydrogen atom or a lower alkyl radical having 1 to 4 carbon atoms or -NH-Rg, W is -COOR7 or another group which can be converted into a carboxyl function, R7 is a lower alkyl radical having 1 to 4 carbon atoms and Rq is an amino protective group and R3 has the above-given meaning^is either a 1) alkylated with a compound of the general formula: rx-a-y (III) in which R^ and A have the above-given meanings and Y is a reactive residue, or a 2) when Z2 is a hydrogen atom, is condensed with a compound of the general formula:- r1-a,-cho (iii1) in which a* is an alkylene radical a shortened by a -CH2- group and R^ has the above-given meani^^^and subsequent to the condensation the resultant double bond is hydrogenated and b) the compound of general formula:- jf 61990,3 ■ - • 1 216830 -67- ' fl R, - A - C - W (IV) I Z2 wherein R^Zj, Zj, A and W have the above mentioned meanings obtained from the above process steps is optionally converted in that, b 1) When Z2 is a hydrogen atom, it is again alkylated with a compound of the general formula R2 - Y (V) in which has the above-given meaning and Y is a reactive group; or b 2) when Z^ is -COOR7 and Z2 is -NH-Rg, the radical Rg is converted in known manner into a radical -CO-R^ or -S02-R3 or b 3) when Z^ is -COOR^ and is a hydrogen atom, the hydrogen atom is exchanged in known manner by a halogen atom with the use of a halogenation agent, subsequently thereto the radical Z^ is converted by decarboxylation into a hydrogen atom and the reactive derivative (IV), in which Z2 is now a halogen atom and Z^ a hydrogen atom, is reacted either with a compound of the general formula:- H- B- R3 (VI) in which B is 0, S or NHS02 and R3 has the above-given meaning, to give a compound of the general formula:- H l R, - A - C - W (IV X I b - r3 wherein R1, R3, A, B and W have the above mentioned meanings or with a compound of the general formula:- 2168 HNR4R5 (VI •) in which and Rg have the above-given meanings, to give a compound of the general formula H I r, - a - c - w (iv") X I nr4r5 wherein Rj, R^, R5, A and W have the above mentioned meanings; or 5 c) aubsequent to the condensation, when c 1) B is a sulphur atom, it is optionally oxidised in known manner to the corresponding sulphoxide or oulphone, or c 2) the reactive derivative (IV), in which 2^ 10 is a hydrogen atom and z2 is a halogen atom, is reacted with sodium sulphite and the compound obtained, in which Z2 is now -SO3H, is converted in known manner into the group -SO2NR4R5 and, subsequent to these optional changes of the compound (IV), the group W and optionally 15 the group Z1 is converted into a free carboxylic acid or into a salt, ester , amide or nitrile thereof; or B) a compound of general formula (IV), in which z^ and Z2 together represent an oxo function, is -fawrat reacted with a reducing ■ agonfe or with an organoraetallic compound 20 of the general formula:- R2 - M in which R2 has the above-given mea alkali metal or alkaline earth metal, m. n St. 216820 (IV) obtained, in which is now a radical R2 and z2 ia a hydroxyl group, is acylated in known manner with a sulphonyl chloride of the general formula R3-SO2CI (VIII) 5 or with a carboxylic acid chloride of the general formula R3-C0Cl (IX) in which R3 has the above-given meaning, and subsequently thereto the group W is optionally converted 10 into a free carboxylic acid group or into a salt, ester, amide or nitrile thereof. 5. A process according to claim 4 for the preparation » of carboxylic acid derivatives, substantially as hereinbefore described and exemplified. 15 6. Carboxylic acid derivatives, whenever prepared by the process according to claim 4 or 5. 7« Pharmaceutical compositions containing at least one compound of general formula (I1) R2 » 1 1 1 O -. J- " A " ? _ COOH * y wherein R'i is hydrogen or an aryl or aryloxy radical unsubstituted or substituted in one or more positions by hydroxyl, halogen, lower alkyl, lower alkoxy, trifluoromethyl, cyano, nitro or amino, whereby the amino group can be substituted once or twice by lower alkyl, R'2 is a hydrogen atom, a lower alkyl radical or the group R'j-A'- wherein R'j has the meaning given above and, when x'is a cyano group, can also be an acylamino or amino group, A' is a straight- o o ?\cszo -70- chained or branched, saturated or unsaturated alkylene radical containing 1 to 18 carbon atoms, and X' is a cyano or carbethoxy radical or a radical of the general formula -B-R3, or -D-NR^Rj, in which B is 0, S, SO, S02, 0(C0), 0S02, NHCO, NHS02 or CO, D is a valency bond, S02 or CO, Rj is an alkyl, trifluoromethyl, cycloalkyl, aralkyl, aralkenyl or aryl radical, the aryl moieties of which can be substituted in one or more positions by hydroxyl, halogen, lower alkyl, lower alkoxy, trifluoromethyl, cyano, nitro or amino, whereby the amino group can be substituted once or twice by lower alkyl, R^ is a hydrogen atom, a lower alkyl radical or an unsubstituted or substituted aryl or aralkyl radical in one or more positions by hydroxyl, halogen, lower alkyl, lower alkoxy, trifluoromethyl, cyano, nitro, or amino, whereby the amino group can be substituted once or twice by lower alkyl, and R5 is a hydrogen atom or a lower alkyl radical or R^ and R5 together form an alkylene chain containing 4 to 6 carbon atoms which can be interrupted by 0, S or NRfi and R6 is a hydrogen atom, a lower alkyl radical or an unsubstituted or substituted phenyl or benzyl radical in one or more positions by hydroxyl, halogen, lower alkyl, lower alkoxy, trifluoromethyl, cyano, nitro or amino whereby the amino group can be substituted once or twice by lower alkyl, as well as of the physiologically acceptable salts, esters, amides and nitriles thereof for combating diabetes, prediabetes, adipositas and atherosclerosis, as well as conventional pharmaceutical carriers and adjuvants. 8. Pharmaceutical compositions containing at least one compound of general formula (I) given in claim i , as well as conventional pharmaceutical carriers and * adjuvants. BOEHRINGER MANNHEIM GmbH By Their Attorneys HENRY HUGHES LTD By:. , AUg*990Z Yt A </div>